Precision pharmacology for Alzheimer's disease

Pharmacological Research

Volumn 130, Issue , 2018, Pages 331-365

  Hampel, Harald ^a,b,c   Vergallo, Andrea ^a,b,c   Aguilar, Lisi Flores ^d   Benda, Norbert ^e   Broich, Karl ^e   Cuello, A Claudio ^d   Cummings, Jeffrey ^f   Dubois, Bruno ^a,b,c   Federoff, Howard J ^g   Fiandaca, Massimo ^h   Genthon, Remy ^a,c   Haberkamp, Marion ^e   Karran, Eric ^i,j,k   Mapstone, Mark ^h   Perry, George ^l   Schneider, Lon S ^m   Welikovitch, Lindsay A ^d   Woodcock, Janet ⁿ   Baldacci, Filippo ^a,b,c,o   Lista, Simone ^a,b,c  

^a SORBONNE UNIVERSITÉ   (France)

^b INSTITUT DU CERVEAU ET DE LA MOELLE ÉPINIÈRE   (France)

^c PITIÉ SALPÊTRIÈRE HOSPITAL   (France)

^d MCGILL UNIVERSITY   (Canada)

^e Federal Institute for Drugs and Medical Devices   (Germany)

^f CLEVELAND CLINIC LOU RUVO CENTER FOR BRAIN HEALTH   (United States)

^g University of California   (United States)

^h UNIVERSITY OF CALIFORNIA   (United States)

ⁱ Foundational Neuroscience Center   (United States)

^j UNIVERSITY COLLEGE LONDON   (United Kingdom)

^k UNIVERSITY OF LEUVEN   (Belgium)

^l University of San Antonio   (United States)

^m UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

ⁿ CENTER FOR DRUG EVALUATION AND RESEARCH   (United States)

^o UNIVERSITY OF PISA   (Italy)

more..

Author keywords

Alzheimer's disease; Clinical trials; Pathophysiology; Pathway based therapy; Precision medicine; Precision pharmacology

Indexed keywords

AMYLOID BETA PROTEIN; AMYLOID PRECURSOR PROTEIN; BIOLOGICAL MARKER; INTERLEUKIN 1BETA; INTERLEUKIN 6; PRESENILIN 1; PRESENILIN 2; TAU PROTEIN; TRANSFORMING GROWTH FACTOR BETA; TUMOR NECROSIS FACTOR; TUMOR NECROSIS FACTOR RECEPTOR ASSOCIATED FACTOR 1; TUMOR NECROSIS FACTOR RECEPTOR ASSOCIATED FACTOR 2;

ALZHEIMER DISEASE; CENTRAL NERVOUS SYSTEM; DISEASE ASSOCIATION; DRUG DEVELOPMENT; GENE INTERACTION; GENOME-WIDE ASSOCIATION STUDY; GENOTYPE ENVIRONMENT INTERACTION; HOMEOSTASIS; HUMAN; MAXIMUM TOLERATED DOSE; METABOLOMICS; MILD COGNITIVE IMPAIRMENT; MOLECULAR INTERACTION; NERVOUS SYSTEM INFLAMMATION; PATHOPHYSIOLOGY; PATIENT SELECTION; PERSONALIZED MEDICINE; PHARMACOLOGY; PRECISION PHARMACOLOGY; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION; SYSTEMS BIOLOGY; TIME; TRANSLATIONAL RESEARCH; TREATMENT FAILURE; ANIMAL; ANTAGONISTS AND INHIBITORS; BLOOD; METABOLISM;

ALZHEIMER DISEASE; AMYLOID BETA-PEPTIDES; ANIMALS; BIOMARKERS; DRUG DISCOVERY; HUMANS; PRECISION MEDICINE; TAU PROTEINS;

EID: 85042621386     PISSN: 10436618     EISSN: 10961186     Source Type: Journal    
DOI: 10.1016/j.phrs.2018.02.014     Document Type: Review

References (313)

1. Hampel, H., Frank, R., Broich, K., Teipel, S.J., Katz, R.G., Hardy, J., Herholz, K., Bokde, A.L.W., Jessen, F., Hoessler, Y.C., Sanhai, W.R., Zetterberg, H., Woodcock, J., Blennow, K., Biomarkers for Alzheimer's disease: academic, industry and regulatory perspectives. Nat. Rev. Drug Discov. 9 (2010), 560–574, 10.1038/nrd3115.
2. Chen, R., Mias, G.I., Li-Pook-Than, J., Jiang, L., Lam, H.Y.K., Chen, R., Miriami, E., Karczewski, K.J., Hariharan, M., Dewey, F.E., Cheng, Y., Clark, M.J., Im, H., Habegger, L., Balasubramanian, S., O'Huallachain, M., Dudley, J.T., Hillenmeyer, S., Haraksingh, R., Sharon, D., Euskirchen, G., Lacroute, P., Bettinger, K., Boyle, A.P., Kasowski, M., Grubert, F., Seki, S., Garcia, M., Whirl-Carrillo, M., Gallardo, M., Blasco, M.A., Greenberg, P.L., Snyder, P., Klein, T.E., Altman, R.B., Butte, A.J., Ashley, E.A., Gerstein, M., Nadeau, K.C., Tang, H., Snyder, M., Personal omics profiling reveals dynamic molecular and medical phenotypes. Cell 148 (2012), 1293–1307, 10.1016/j.cell.2012.02.009.
3. Hampel, H., O'Bryant, S., Durrleman, E., Younesi, K., Escott-Price, V., Corvol, K., Broich, B., Lista, S., for the A.P.M. Initiative, A Precision Medicine Initiative for Alzheimer's disease: the road ahead to biomarker-guided integrative disease modeling. Climacteric, 2017, 1–12, 10.1080/13697137.2017.1287866.
4. Hampel, H., O'Bryant, S.E., Castrillo, J.I., Ritchie, C., Rojkova, K., Broich, K., Benda, N., Nisticò, R., Frank, R.A., Dubois, B., Escott-Price, V., Lista, S., PRECISION MEDICINE – The golden gate for detection. Treat. Prev.f Alzheimer's Dis., 2016, 10.14283/jpad.2016.112.
5. Iyengar, R., Zhao, S., Chung, S.-W., Mager, D.E., Gallo, J.M., Merging systems biology with pharmacodynamics. Sci. Transl. Med., 4, 2012, 10.1126/scitranslmed.3003563 126ps7.
6. Harrold, J.M., Ramanathan, M., Mager, D.E., Network-based approaches in drug discovery and early development. Clin. Pharmacol. Ther. 94 (2013), 651–658, 10.1038/clpt.2013.176.
7. Zhao, S., Iyengar, R., Systems pharmacology: network analysis to identify multiscale mechanisms of drug action. Annu. Rev. Pharmacol. Toxicol. 52 (2012), 505–521, 10.1146/annurev-pharmtox-010611-134520.
8. Keiser, M.J., Roth, B.L., Armbruster, B.N., Ernsberger, P., Irwin, J.J., Shoichet, B.K., Relating protein pharmacology by ligand chemistry. Nat. Biotechnol. 25 (2007), 197–206, 10.1038/nbt1284.
9. Berg, J., Gene-environment interplay. Science, 354, 2016, 15, 10.1126/science.aal0219.
10. Cavedo, E., Lista, S., Khachaturian, Z., Aisen, P., Amouyel, P., Herholz, K., Jack, C.R., Sperling, R., Cummings, J., Blennow, K., O'Bryant, S., Frisoni, G.B., Khachaturian, A., Kivipelto, M., Klunk, W., Broich, K., Andrieu, S., de Schotten, M.T., Mangin, J.-F., Lammertsma, A.A., Johnson, K., Teipel, S., Drzezga, A., Bokde, A., Colliot, O., Bakardjian, H., Zetterberg, H., Dubois, B., Vellas, B., Schneider, L.S., Hampel, H., The road ahead to cure Alzheimer's disease: development of biological markers and neuroimaging methods for prevention trials across all stages and target populations. J. Prev. Alzheimers Dis. 1 (2014), 181–202, 10.14283/jpad.2014.32.
11. Bulyk, M.L., Walhout, A.J.M., Chapter 4 – gene regulatory networks. Handb. Syst. Biol., 2013, Academic Press, San Diego, 65–88, 10.1016/B978-0-12-385944-0.00004-6.
12. Power, A., Berger, A.C., Ginsburg, G.S., Genomics-enabled drug repositioning and repurposing: insights from an IOM Roundtable activity. JAMA 311 (2014), 2063–2064, 10.1001/jama.2014.3002.
13. Padmanabhan, K., Shpanskaya, K., Bello, G., Doraiswamy, P.M., Samatova, N.F., Toward personalized network biomarkers in Alzheimer's disease: computing individualized genomic and protein crosstalk maps. Front. Aging Neurosci., 9, 2017, 315, 10.3389/fnagi.2017.00315.
14. Vanneman, M., Dranoff, G., Combining immunotherapy and targeted therapies in cancer treatment. Nat. Rev. Cancer. 12 (2012), 237–251, 10.1038/nrc3237.
15. Vogel, C., Marcotte, E.M., Insights into the regulation of protein abundance from proteomic and transcriptomic analyses. Nat. Rev. Genet. 13 (2012), 227–232, 10.1038/nrg3185.
16. Hampel, H., Lista, S., Teipel, S.J., Garaci, F., Nisticò, R., Blennow, K., Zetterberg, H., Bertram, L., Duyckaerts, C., Bakardjian, H., Drzezga, A., Colliot, O., Epelbaum, S., Broich, K., Lehéricy, S., Brice, A., Khachaturian, Z.S., Aisen, P.S., Dubois, B., Perspective on future role of biological markers in clinical therapy trials of Alzheimer's disease: a long-range point of viewbeyond 2020. Biochem. Pharmacol. 88 (2014), 426–449, 10.1016/j.bcp.2013.11.009.
17. Miller, J.A., Woltjer, R.L., Goodenbour, J.M., Horvath, S., Geschwind, D.H., Genes and pathways underlying regional and cell type changes in Alzheimer's disease. Genome Med., 5, 2013, 48, 10.1186/gm452.
18. Blennow, K., Hampel, H., Weiner, M., Zetterberg, H., Cerebrospinal fluid and plasma biomarkers in Alzheimer disease. Nat. Rev. Neurol. 6 (2010), 131–144, 10.1038/nrneurol.2010.4.
19. Guo, J.L., Lee, V.M.Y., Cell-to-cell transmission of pathogenic proteins in neurodegenerative diseases. Nat. Med. 20 (2014), 130–138, 10.1038/nm.3457.
20. Rawji, K.S., Mishra, M.K., Michaels, N.J., Rivest, S., Stys, P.K., Yong, V.W., Immunosenescence of microglia and macrophages: impact on the ageing central nervous system. Brain J. Neurol. 139 (2016), 653–661, 10.1093/brain/awv395.
21. Tarasoff-Conway, J.M., Carare, R.O., Osorio, R.S., Glodzik, L., Butler, T., Fieremans, E., Axel, L., Rusinek, H., Nicholson, C., Zlokovic, B.V., Frangione, B., Blennow, K., Ménard, J., Zetterberg, H., Wisniewski, T., de Leon, M.J., Clearance systems in the brain-implications for Alzheimer disease. Nat. Rev. Neurol. 11 (2015), 457–470, 10.1038/nrneurol.2015.119.
22. Louveau, A., Smirnov, I., Keyes, T.J., Eccles, J.D., Rouhani, S.J., Peske, J.D., Derecki, N.C., Castle, D., Mandell, J.W., Lee, K.S., Harris, T.H., Kipnis, J., Structural and functional features of central nervous system lymphatic vessels. Nature 523 (2015), 337–341, 10.1038/nature14432.
23. Kenyon, C.J., The genetics of ageing. Nature 464 (2010), 504–512, 10.1038/nature08980.
24. Fontana, L., Partridge, L., Longo, V.D., Extending healthy life span–from yeast to humans. Science 328 (2010), 321–326, 10.1126/science.1172539.
25. Lu, T., Aron, L., Zullo, J., Pan, Y., Kim, H., Chen, Y., Yang, T.-H., Kim, H.-M., Drake, D., Liu, X.S., Bennett, D.A., Colaiácovo, M.P., Yankner, B.A., REST and stress resistance in ageing and Alzheimer's disease. Nature 507 (2014), 448–454, 10.1038/nature13163.
26. Mair, W., Morantte, I., Rodrigues, A.P.C., Manning, G., Montminy, M., Shaw, R.J., Dillin, A., Lifespan extension induced by AMPK and calcineurin is mediated by CRTC-1 and CREB. Nature 470 (2011), 404–408, 10.1038/nature09706.
27. Harrison, D.E., Strong, R., Sharp, Z.D., Nelson, J.F., Astle, C.M., Flurkey, K., Nadon, N.L., Wilkinson, J.E., Frenkel, K., Carter, C.S., Pahor, M., Javors, M.A., Fernandez, E., Miller, R.A., Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature 460 (2009), 392–395, 10.1038/nature08221.
28. Camandola, S., Mattson, M.P., Brain metabolism in health, aging, and neurodegeneration. EMBO J. 36 (2017), 1474–1492, 10.15252/embj.201695810.
29. Ramos, F.J., Kaeberlein, M., Ageing A healthy diet for stem cells. Nature 486 (2012), 477–478, 10.1038/486477a.
30. Eisenberg, D., Jucker, M., The amyloid state of proteins in human diseases. Cell 148 (2012), 1188–1203, 10.1016/j.cell.2012.02.022.
31. Balch, W.E., Morimoto, R.I., Dillin, A., Kelly, J.W., Adapting proteostasis for disease intervention. Science 319 (2008), 916–919, 10.1126/science.1141448.
32. Villeda, S.A., Luo, J., Mosher, K.I., Zou, B., Britschgi, M., Bieri, G., Stan, T.M., Fainberg, N., Ding, Z., Eggel, A., Lucin, K.M., Czirr, E., Park, J.-S., Couillard-Després, S., Aigner, L., Li, G., Peskind, E.R., Kaye, J.A., Quinn, J.F., Galasko, D.R., Xie, X.S., Rando, T.A., Wyss-Coray, T., The ageing systemic milieu negatively regulates neurogenesis and cognitive function. Nature 477 (2011), 90–94, 10.1038/nature10357.
33. Hoeijmakers, J.H.J., DNA damage, aging, and cancer. N. Engl. J. Med. 361 (2009), 1475–1485, 10.1056/NEJMra0804615.
34. Selman, C., Tullet, J.M.A., Wieser, D., Irvine, E., Lingard, S.J., Choudhury, A.I., Claret, M., Al-Qassab, H., Carmignac, D., Ramadani, F., Woods, A., Robinson, I.C.A., Schuster, E., Batterham, R.L., Kozma, S.C., Thomas, G., Carling, D., Okkenhaug, K., Thornton, J.M., Partridge, L., Gems, D., Withers, D.J., Ribosomal protein S6 kinase 1 signaling regulates mammalian life span. Science 326 (2009), 140–144, 10.1126/science.1177221.
35. Rolyan, H., Scheffold, A., Heinrich, A., Begus-Nahrmann, Y., Langkopf, B.H., Hölter, S.M., Vogt-Weisenhorn, D.M., Liss, B., Wurst, W., Lie, D.C., Thal, D.R., Biber, K., Rudolph, K.L., Telomere shortening reduces Alzheimer's disease amyloid pathology in mice. Brain J. Neurol. 134 (2011), 2044–2056, 10.1093/brain/awr133.
36. Garinis, G.A., van der Horst, G.T.J., Vijg, J., Hoeijmakers, J.H.J., DNA damage and ageing: new-age ideas for an age-old problem. Nat. Cell Biol. 10 (2008), 1241–1247, 10.1038/ncb1108-1241.
37. Ron, D., Walter, P., Signal integration in the endoplasmic reticulum unfolded protein response. Nat. Rev. Mol. Cell Biol. 8 (2007), 519–529, 10.1038/nrm2199.
38. Cohen, P., Frame, S., The renaissance of GSK3. Nat. Rev. Mol. Cell Biol. 2 (2001), 769–776, 10.1038/35096075.
39. Natarajan, M., Lin, K.-M., Hsueh, R.C., Sternweis, P.C., Ranganathan, R., A global analysis of cross-talk in a mammalian cellular signalling network. Nat. Cell Biol. 8 (2006), 571–580, 10.1038/ncb1418.
40. Matsunaga, S., Kishi, T., Annas, P., Basun, H., Hampel, H., Iwata, N., Lithium as a treatment for Alzheimer's disease: a systematic review and meta-analysis. J. Alzheimers Dis. JAD 48 (2015), 403–410, 10.3233/JAD-150437.
41. Benjamin, D., Colombi, M., Moroni, C., Hall, M.N., Rapamycin passes the torch: a new generation of mTOR inhibitors. Nat. Rev. Drug Discov. 10 (2011), 868–880, 10.1038/nrd3531.
42. O'Bryant, S.E., Mielke, M.M., Rissman, R.A., Lista, S., Vanderstichele, H., Zetterberg, H., Lewczuk, P., Posner, H., Hall, J., Johnson, L., Fong, Y.-L., Luthman, J., Jeromin, A., Batrla-Utermann, R., Villarreal, A., Britton, G., Snyder, P.J., Henriksen, K., Grammas, P., Gupta, V., Martins, R., Hampel, H., Biofluid based biomarker professional interest area, blood-based biomarkers in Alzheimer disease: current state of the science and a novel collaborative paradigm for advancing from discovery to clinict. Alzheimers Dement. J. Alzheimers Assoc. 13 (2017), 45–58, 10.1016/j.jalz.2016.09.014.
43. Gal, A.A., In search of the origins of modern surgical pathology. Adv. Anat. Pathol. 8 (2001), 1–13.
44. Alzheimer, A., Stelzmann, R.A., Schnitzlein, H.N., Murtagh, F.R., An english translation of Alzheimer's 1907 paper, uber eine eigenartige erkankung der hirnrinde. Clin. Anat. N.Y. 8 (1995), 429–431, 10.1002/ca.980080612.
45. Ogomori, K., Kitamoto, T., Tateishi, J., Sato, Y., Suetsugu, M., Abe, M., Beta-protein amyloid is widely distributed in the central nervous system of patients with Alzheimer's disease. Am. J. Pathol. 134 (1989), 243–251.
46. Braak, H., Braak, E., Demonstration of amyloid deposits and neurofibrillary changes in whole brain sections. Brain Pathol. Zurich Switz. 1 (1991), 213–216.
47. Crowther, T., Goedert, M., Wischik, C.M., The repeat region of microtubule-associated protein tau forms part of the core of the paired helical filament of Alzheimer's disease. Ann. Med. 21 (1989), 127–132.
48. Foley, P., Lipids in Alzheimer's disease: a century-old story. Biochim. Biophys. Acta 2010 (1801), 750–753, 10.1016/j.bbalip.2010.05.004.
49. Di Paolo, G., Kim, T.-W., Linking lipids to Alzheimer's disease: cholesterol and beyond. Nat. Rev. Neurosci. 12 (2011), 284–296, 10.1038/nrn3012.
50. Bateman, R.J., Xiong, C., Benzinger, T.L.S., Fagan, A.M., Goate, A., Fox, N.C., Marcus, D.S., Cairns, N.J., Xie, X., Blazey, T.M., Holtzman, D.M., Santacruz, A., Buckles, V., Oliver, A., Moulder, K., Aisen, P.S., Ghetti, B., Klunk, W.E., McDade, E., Martins, R.N., Masters, C.L., Mayeux, R., Ringman, J.M., Rossor, M.N., Schofield, P.R., Sperling, R.A., Salloway, S., Morris, J.C., Dominantly Inherited Alzheimer Network, Clinical and biomarker changes in dominantly inherited Alzheimer's disease. N. Engl. J. Med. 367 (2012), 795–804, 10.1056/NEJMoa1202753.
51. Braak, H., Braak, E., Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. (Berl) 82 (1991), 239–259.
52. Hardy, J.A., Higgins, G.A., Alzheimer's disease: the amyloid cascade hypothesis. Science 256 (1992), 184–185.
53. Selkoe, D.J., Toward a comprehensive theory for Alzheimer's disease. Hypothesis: Alzheimer's disease is caused by the cerebral accumulation and cytotoxicity of amyloid beta-protein. Ann. N. Y. Acad. Sci. 924 (2000), 17–25.
54. Cummings, J.L., Morstorf, T., Zhong, K., Alzheimer's disease drug-development pipeline: few candidates, frequent failures. Alzheimers Res. Ther., 6, 2014, 37, 10.1186/alzrt269.
55. Hardy, J., Membrane damage is at the core of Alzheimer's disease. Lancet Neurol., 16, 2017, 342, 10.1016/S1474-4422(17)30091-1.
56. Sperling, R.A., Aisen, P.S., Beckett, L.A., Bennett, D.A., Craft, S., Fagan, A.M., Iwatsubo, T., Jack, C.R., Kaye, J., Montine, T.J., Park, D.C., Reiman, E.M., Rowe, C.C., Siemers, E., Stern, Y., Yaffe, K., Carrillo, M.C., Thies, B., Morrison-Bogorad, M., Wagster, M.V., Phelps, C.H., Toward defining the preclinical stages of Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. J. Alzheimers Assoc. 7 (2011), 280–292, 10.1016/j.jalz.2011.03.003.
57. Pfeiffer, R.F., Neuroinflammation and Parkinson disease: the silent battleground. Neurology 73 (2009), 1434–1435, 10.1212/WNL.0b013e3181c2f07d.
58. Mattsson, N., Bremell, D., Anckarsäter, R., Blennow, K., Anckarsäter, H., Zetterberg, H., Hagberg, L., Neuroinflammation in Lyme neuroborreliosis affects amyloid metabolism. BMC Neurol., 10, 2010, 51, 10.1186/1471-2377-10-51.
59. Heneka, M.T., Carson, M.J., El Khoury, J., Landreth, G.E., Brosseron, F., Feinstein, D.L., Jacobs, A.H., Wyss-Coray, T., Vitorica, J., Ransohoff, R.M., Herrup, K., Frautschy, S.A., Finsen, B., Brown, G.C., Verkhratsky, A., Yamanaka, K., Koistinaho, J., Latz, E., Halle, A., Petzold, G.C., Town, T., Morgan, D., Shinohara, M.L., Perry, V.H., Holmes, C., Bazan, N.G., Brooks, D.J., Hunot, S., Joseph, B., Deigendesch, N., Garaschuk, O., Boddeke, E., Dinarello, C.A., Breitner, J.C., Cole, G.M., Golenbock, D.T., Kummer, M.P., Neuroinflammation in Alzheimer's disease. Lancet Neurol. 14 (2015), 388–405, 10.1016/S1474-4422(15)70016-5.
60. Filippi, M., Agosta, F., Does neuroinflammation sustain neurodegeneration in ALS?. Neurology 87 (2016), 2508–2509, 10.1212/WNL.0000000000003441.
61. Malkki, H., Multiple sclerosis: coagulation factors could mediate neuroinflammation in multiple sclerosis. Nat. Rev. Neurol., 12, 2016, 679, 10.1038/nrneurol.2016.175.
62. Simon, D.W., McGeachy, M.J., Bayır, H., Clark, R.S.B., Loane, D.J., Kochanek, P.M., The far-reaching scope of neuroinflammation after traumatic brain injury. Nat. Rev. Neurol., 13, 2017, 572, 10.1038/nrneurol.2017.116.
63. Rossi, S., Studer, V., Motta, C., Polidoro, S., Perugini, J., Macchiarulo, G., Giovannetti, A.M., Pareja-Gutierrez, L., Calò, A., Colonna, I., Furlan, R., Martino, G., Centonze, D., Neuroinflammation drives anxiety and depression in relapsing-remitting multiple sclerosis. Neurology 89 (2017), 1338–1347, 10.1212/WNL.0000000000004411.
64. Baldacci, F., Lista, S., Cavedo, E., Bonuccelli, U., Hampel, H., Diagnostic function of the neuroinflammatory biomarker YKL-40 in Alzheimer's disease and other neurodegenerative diseases, Expert Rev. Proteomics 14 (2017), 285–299, 10.1080/14789450.2017.1304217.
65. Glass, C.K., Saijo, K., Winner, B., Marchetto, M.C., Gage, F.H., Mechanisms underlying inflammation in neurodegeneration. Cell 140 (2010), 918–934, 10.1016/j.cell.2010.02.016.
66. Akiyama, H., Barger, S., Barnum, S., Bradt, B., Bauer, J., Cole, G.M., Cooper, N.R., Eikelenboom, P., Emmerling, M., Fiebich, B.L., Finch, C.E., Frautschy, S., Griffin, W.S., Hampel, H., Hull, M., Landreth, G., Lue, L., Mrak, R., Mackenzie, I.R., McGeer, P.L., O'Banion, M.K., Pachter, J., Pasinetti, G., Plata-Salaman, C., Rogers, J., Rydel, R., Shen, Y., Streit, W., Strohmeyer, R., Tooyoma, I., Van Muiswinkel, F.L., Veerhuis, R., Walker, D., Webster, S., Wegrzyniak, B., Wenk, G., Wyss-Coray, T., Inflammation and Alzheimer's disease. Neurobiol. Aging 21 (2000), 383–421.
67. Duong, T., Nikolaeva, M., Acton, P.J., C-reactive protein-like immunoreactivity in the neurofibrillary tangles of Alzheimer's disease. Brain Res. 749 (1997), 152–156.
68. Iwamoto, N., Nishiyama, E., Ohwada, J., Arai, H., Demonstration of CRP immunoreactivity in brains of Alzheimer's disease: immunohistochemical study using formic acid pretreatment of tissue sections. Neurosci. Lett. 177 (1994), 23–26.
69. McGeer, P.L., McGeer, E.G., Inflammation, autotoxicity and Alzheimer disease. Neurobiol. Aging 22 (2001), 799–809.
70. van Dam, A.M., Brouns, M., Louisse, S., Berkenbosch, F., Appearance of interleukin-1 in macrophages and in ramified microglia in the brain of endotoxin-treated rats: a pathway for the induction of non-specific symptoms of sickness?. Brain Res. 588 (1992), 291–296.
71. Hickman, S.E., El Khoury, J., TREM2 and the neuroimmunology of Alzheimer's disease. Biochem. Pharmacol. 88 (2014), 495–498, 10.1016/j.bcp.2013.11.021.
72. Lill, C.M., Rengmark, A., Pihlstrøm, L., Fogh, I., Shatunov, A., Sleiman, P.M., Wang, L.-S., Liu, T., Lassen, C.F., Meissner, E., Alexopoulos, P., Calvo, A., Chio, A., Dizdar, N., Faltraco, F., Forsgren, L., Kirchheiner, J., Kurz, A., Larsen, J.P., Liebsch, M., Linder, J., Morrison, K.E., Nissbrandt, H., Otto, M., Pahnke, J., Partch, A., Restagno, G., Rujescu, D., Schnack, C., Shaw, C.E., Shaw, P.J., Tumani, H., Tysnes, O.-B., Valladares, O., Silani, V., van den Berg, L.H., van Rheenen, W., Veldink, J.H., Lindenberger, U., Steinhagen-Thiessen, E., SLAGEN, Consortium, Teipel, S., Perneczky, R., Hakonarson, H., Hampel, H., von Arnim, C.A.F., Olsen, J.H., Van Deerlin, V.M., Al-Chalabi, A., Toft, M., Ritz, B., Bertram, L., The role of TREM2 R47H as a risk factor for Alzheimer's disease, frontotemporal lobar degeneration, amyotrophic lateral sclerosis, and Parkinson's disease. Alzheimers Dement. J. Alzheimers Assoc. 11 (2015), 1407–1416, 10.1016/j.jalz.2014.12.009.
73. Sherva, R., Farrer, L.A., Power and pitfalls of the genome-wide association study approach to identify genes for Alzheimer's disease. Curr. Psychiatry Rep. 13 (2011), 138–146, 10.1007/s11920-011-0184-4.
74. Villegas-Llerena, C., Phillips, A., Garcia-Reitboeck, P., Hardy, J., Pocock, J.M., Microglial genes regulating neuroinflammation in the progression of Alzheimer's disease. Curr. Opin. Neurobiol. 36 (2016), 74–81, 10.1016/j.conb.2015.10.004.
75. Zhang, Z.-G., Li, Y., Ng, C.T., Song, Y.-Q., Inflammation in Alzheimer's disease and molecular genetics: recent update. Arch. Immunol. Ther. Exp. (Warsz.) 63 (2015), 333–344, 10.1007/s00005-015-0351-0.
76. Jonsson, T., Stefansson, H., Steinberg, S., Jonsdottir, I., Jonsson, P.V., Snaedal, J., Bjornsson, S., Huttenlocher, J., Levey, A.I., Lah, J.J., Rujescu, D., Hampel, H., Giegling, I., Andreassen, O.A., Engedal, K., Ulstein, I., Djurovic, S., Ibrahim-Verbaas, C., Hofman, A., Ikram, M.A., van Duijn, C.M., Thorsteinsdottir, U., Kong, A., Stefansson, K., Variant of TREM2 associated with the risk of Alzheimer's disease. N. Engl. J. Med. 368 (2013), 107–116, 10.1056/NEJMoa1211103.
77. Guerreiro, R., Wojtas, A., Bras, J., Carrasquillo, M., Rogaeva, E., Majounie, E., Cruchaga, C., Sassi, C., Kauwe, J.S.K., Younkin, S., Hazrati, L., Collinge, J., Pocock, J., Lashley, T., Williams, J., Lambert, J.-C., Amouyel, P., Goate, A., Rademakers, R., Morgan, K., Powell, J., St George-Hyslop, P., Singleton, A., Hardy, J., Alzheimer genetic analysis group, TREM2 variants in Alzheimer's disease. N. Engl. J. Med. 368 (2013), 117–127, 10.1056/NEJMoa1211851.
78. Neumann, H., Daly, M.J., Variant TREM2 as risk factor for Alzheimer's disease. N. Engl. J. Med. 368 (2013), 182–184, 10.1056/NEJMe1213157.
79. van Duijn, C.M., Hofman, A., Nagelkerken, L., Serum levels of interleukin-6 are not elevated in patients with Alzheimer's disease. Neurosci. Lett. 108 (1990), 350–354.
80. Singh, V.K., Guthikonda, P., Circulating cytokines in Alzheimer's disease. J. Psychiatr. Res. 31 (1997), 657–660.
81. Lanzrein, A.S., Johnston, C.M., Perry, V.H., Jobst, K.A., King, E.M., Smith, A.D., Longitudinal study of inflammatory factors in serum, cerebrospinal fluid, and brain tissue in Alzheimer disease: interleukin-1beta, interleukin-6 interleukin-1 receptor antagonist, tumor necrosis factor-alpha, the soluble tumor necrosis factor receptors I and II, and alpha1-antichymotrypsin. Alzheimer Dis. Assoc. Disord. 12 (1998), 215–227.
82. Bagli, M., Papassotiropoulos, A., Hampel, H., Becker, K., Jessen, F., Bürger, K., Ptok, U., Rao, M.L., Möller, H.-J., Maier, W., Heun, R., Polymorphisms of the gene encoding the inflammatory cytokine interleukin-6 determine the magnitude of the increase in soluble interleukin-6 receptor levels in Alzheimer's disease. Results of a pilot study. Eur. Arch. Psychiatry Clin. Neurosci. 253 (2003), 44–48, 10.1007/s00406-003-0405-x.
83. Richartz, E., Stransky, E., Batra, A., Simon, P., Lewczuk, P., Buchkremer, G., Bartels, M., Schott, K., Decline of immune responsiveness: a pathogenetic factor in Alzheimer's disease?. J. Psychiatr. Res. 39 (2005), 535–543, 10.1016/j.jpsychires.2004.12.005.
84. Dursun, E., Gezen-Ak, D., Hanağası, H., Bilgiç, B., Lohmann, E., Ertan, S., İ. Atasoy, L., Alaylıoğlu Ö, S., Önal, B., Gündüz, A., Apaydın, H., Kızıltan, G., Ulutin, T., Gürvit, H., Yılmazer, S., The interleukin 1 alpha, interleukin 1 beta, interleukin 6 and alpha-2-macroglobulin serum levels in patients with early or late onset Alzheimerğs disease, mild cognitive impairment or Parkinsonğs disease. J. Neuroimmunol. 283 (2015), 50–57, 10.1016/j.jneuroim.2015.04.014.
85. Swardfager, W., Lanctôt, K., Rothenburg, L., Wong, A., Cappell, J., Herrmann, N., A meta-analysis of cytokines in Alzheimer's disease. Biol. Psychiatry 68 (2010), 930–941, 10.1016/j.biopsych.2010.06.012.
86. Shen, Y., Wang, H., Sun, Q., Yao, H., Keegan, A.P., Mullan, M., Wilson, J., Lista, S., Leyhe, T., Laske, C., Rujescu, D., Levey, A., Wallin, A., Blennow, K., Li, R., Hampel, H., Increased plasma beta-secretase 1 may predict conversion to Alzheimer's disease dementia in individuals with mild cognitive impairment. Biol. Psychiatry 83:5 (2018), 447–455, 10.1016/j.biopsych.2017.02.007.
87. Li, R., Yang, L., Lindholm, K., Konishi, Y., Yue, X., Hampel, H., Zhang, D., Shen, Y., Tumor necrosis factor death receptor signaling cascade is required for amyloid-beta protein-induced neuron death. J. Neurosci. 24 (2004), 1760–1771, 10.1523/JNEUROSCI.4580-03.2004.
88. He, P., Zhong, Z., Lindholm, K., Berning, L., Lee, W., Lemere, C., Staufenbiel, M., Li, R., Shen, Y., Deletion of tumor necrosis factor death receptor inhibits amyloid beta generation and prevents learning and memory deficits in Alzheimer's mice. J. Cell Biol. 178 (2007), 829–841, 10.1083/jcb.200705042.
89. Cheng, X., Yang, L., He, P., Li, R., Shen, Y., Differential activation of tumor necrosis factor receptors distinguishes between brains from Alzheimer's disease and non-demented patients. J. Alzheimers Dis. JAD 19 (2010), 621–630, 10.3233/JAD-2010-1253.
90. Jiang, H., Hampel, H., Prvulovic, D., Wallin, A., Blennow, K., Li, R., Shen, Y., Elevated CSF levels of TACE activity and soluble TNF receptors in subjects with mild cognitive impairment and patients with Alzheimer's disease. Mol. Neurodegener., 6, 2011, 69, 10.1186/1750-1326-6-69.
91. Hampel, H., Teipel, S.J., Padberg, F., Haslinger, A., Riemenschneider, M., Schwarz, M.J., Kötter, H.U., Scheloske, M., Buch, K., Stübner, S., Dukoff, R., Lasser, R., Müller, N., Sunderland, T., Rapoport, S.I., Möller, H.J., Discriminant power of combined cerebrospinal fluid tau protein and of the soluble interleukin-6 receptor complex in the diagnosis of Alzheimer's disease. Brain Res. 823 (1999), 104–112.
92. Hampel, H., Sunderland, T., Kötter, H.U., Schneider, C., Teipel, S.J., Padberg, F., Dukoff, R., Levy, J., Möller, H.J., Decreased soluble interleukin-6 receptor in cerebrospinal fluid of patients with Alzheimerös disease. Brain Res. 780 (1998), 356–359.
93. Tan, Z.S., Beiser, A.S., Vasan, R.S., Roubenoff, R., Dinarello, C.A., Harris, T.B., Benjamin, E.J., Au, R., Kiel, D.P., Wolf, P.A., Seshadri, S., Inflammatory markers and the risk of Alzheimer disease: the Framingham Study. Neurology 68 (2007), 1902–1908, 10.1212/01.wnl.0000263217.36439.da.
94. Baldacci, F., Toschi, N., Lista, S., Zetterberg, H., Blennow, K., Kilimann, I., Teipel, S., Cavedo, E., Dos Santos, A.M., Epelbaum, S., Lamari, F., Dubois, B., Floris, R., Garaci, F., Bonuccelli, U., Hampel, H., Two-level diagnostic classification using cerebrospinal fluid YKL-40 in Alzheimer's disease. Alzheimers Dement. 13:9 (2017), 993–1003, 10.1016/j.jalz.2017.01.021.
95. Jones, D.P., Sequencing the exposome: a call to action. Toxicol. Rep. 3 (2016), 29–45, 10.1016/j.toxrep.2015.11.009.
96. Yugi, K., Kubota, H., Hatano, A., Kuroda, S., Trans-omics: how to reconstruct biochemical networks across multiple omic layers. Trends Biotechnol. 34 (2016), 276–290, 10.1016/j.tibtech.2015.12.013.
97. Barba, I., Fernandez-Montesinos, R., Garcia-Dorado, D., Pozo, D., Alzheimer's disease beyond the genomic era: nuclear magnetic resonance (NMR) spectroscopy-based metabolomics. J. Cell. Mol. Med. 12 (2008), 1477–1485, 10.1111/j.1582-4934.2008.00385.x.
98. Zhang, A., Sun, H., Wang, P., Han, Y., Wang, X., Modern analytical techniques in metabolomics analysis. Analyst 137 (2012), 293–300, 10.1039/c1an15605e.
99. Sato, Y., Suzuki, I., Nakamura, T., Bernier, F., Aoshima, K., Oda, Y., Identification of a new plasma biomarker of Alzheimer's disease using metabolomics technology. J. Lipid Res. 53 (2012), 567–576, 10.1194/jlr.M022376.
100. Trushina, E., Dutta, T., Persson, X.-M.T., Mielke, M.M., Petersen, R.C., Identification of altered metabolic pathways in plasma and CSF in mild cognitive impairment and Alzheimer's disease using metabolomics. PLoS One, 8, 2013, e63644, 10.1371/journal.pone.0063644.
101. Wang, G., Zhou, Y., Huang, F.-J., Tang, H.-D., Xu, X.-H., Liu, J.-J., Wang, Y., Deng, Y.-L., Ren, R.-J., Xu, W., Ma, J.-F., Zhang, Y.-N., Zhao, A.-H., Chen, S.-D., Jia, W., Plasma metabolite profiles of Alzheimer's disease and mild cognitive impairment. J. Proteome Res. 13 (2014), 2649–2658, 10.1021/pr5000895.
102. Graham, S.F., Chevallier, O.P., Elliott, C.T., Hölscher, C., Johnston, J., McGuinness, B., Kehoe, P.G., Passmore, A.P., Green, B.D., Untargeted metabolomic analysis of human plasma indicates differentially affected polyamine and L-arginine metabolism in mild cognitive impairment subjects converting to Alzheimer's disease. PLoS One, 10, 2015, e0119452, 10.1371/journal.pone.0119452.
103. González-Domínguez, R., Rupérez, F.J., García-Barrera, T., Barbas, C., Gómez-Ariza, J.L., Metabolomic-driven elucidation of serum disturbances associated with Alzheimer's disease and mild cognitive impairment. Curr. Alzheimer Res. 13 (2016), 641–653.
104. Whiley, L., Sen, A., Heaton, J., Proitsi, P., García-Gómez, D., Leung, R., Smith, N., Thambisetty, M., Kloszewska, I., Mecocci, P., Soininen, H., Tsolaki, M., Vellas, B., Lovestone, S., Legido-Quigley, C., AddNeuroMed Consortium, Evidence of altered phosphatidylcholine metabolism in Alzheimer's disease. Neurobiol. Aging 35 (2014), 271–278, 10.1016/j.neurobiolaging.2013.08.001.
105. Klavins, K., Koal, T., Dallmann, G., Marksteiner, J., Kemmler, G., Humpel, C., The ratio of phosphatidylcholines to lysophosphatidylcholines in plasma differentiates healthy controls from patients with Alzheimer's disease and mild cognitive impairment. Alzheimers Dement. Amst. Neth. 1 (2015), 295–302, 10.1016/j.dadm.2015.05.003.
106. Mapstone, M., Cheema, A.K., Fiandaca, M.S., Zhong, X., Mhyre, T.R., MacArthur, L.H., Hall, W.J., Fisher, S.G., Peterson, D.R., Haley, J.M., Nazar, M.D., Rich, S.A., Berlau, D.J., Peltz, C.B., Tan, M.T., Kawas, C.H., Federoff, H.J., Plasma phospholipids identify antecedent memory impairment in older adults. Nat. Med. 20 (2014), 415–418, 10.1038/nm.3466.
107. Fiandaca, M.S., Zhong, X., Cheema, A.K., Orquiza, M.H., Chidambaram, S., Tan, M.T., Gresenz, C.R., FitzGerald, K.T., Nalls, M.A., Singleton, A.B., Mapstone, M., Federoff, H.J., Plasma 24-metabolite panel predicts preclinical transition to clinical stages of Alzheimer's disease. Front. Neurol., 6, 2015, 237, 10.3389/fneur.2015.00237.
108. Hartmann, T., van Wijk, N., Wurtman, R.J., Olde Rikkert, M.G.M., Sijben, J.W.C., Soininen, H., Vellas, B., Scheltens, P., A nutritional approach to ameliorate altered phospholipid metabolism in Alzheimer's disease. J. Alzheimers Dis. JAD 41 (2014), 715–717, 10.3233/JAD-141137.
109. Fiandaca, M.S., Mapstone, M.E., Cheema, A.K., Federoff, H.J., The critical need for defining preclinical biomarkers in Alzheimer's disease. Alzheimers Dement. J. Alzheimers Assoc. 10 (2014), S196–S212, 10.1016/j.jalz.2014.04.015.
110. Wyss-Coray, T., Mucke, L., Inflammation in neurodegenerative disease–a double-edged sword. Neuron 35 (2002), 419–432.
111. Weninger, S.C., Yankner, B.A., Inflammation and Alzheimer disease: the good, the bad, and the ugly. Nat. Med. 7 (2001), 527–528, 10.1038/87839.
112. Cuello, A.C., Early and late CNS inflammation in Alzheimer's disease: two extremes of a continuum?. Trends Pharmacol. Sci. 38 (2017), 956–966, 10.1016/j.tips.2017.07.005.
113. McGeer, P.L., McGeer, E., Rogers, J., Sibley, J., Anti-inflammatory drugs and Alzheimer disease. Lancet Lond. Engl., 335, 1990, 1037.
114. McGeer, P.L., McGeer, E.G., The amyloid cascade-inflammatory hypothesis of Alzheimer disease: implications for therapy. Acta Neuropathol. (Berl.) 126 (2013), 479–497, 10.1007/s00401-013-1177-7.
115. Miguel-Álvarez, M., Santos-Lozano, A., Sanchis-Gomar, F., Fiuza-Luces, C., Pareja-Galeano, H., Garatachea, N., Lucia, A., Non-steroidal anti-inflammatory drugs as a treatment for Alzheimer's disease: a systematic review and meta-analysis of treatment effect. Drugs Aging 32 (2015), 139–147, 10.1007/s40266-015-0239-z.
116. Gupta, P.P., Pandey, R.D., Jha, D., Shrivastav, V., Kumar, S., Role of traditional nonsteroidal anti-inflammatory drugs in Alzheimer's disease: a meta-analysis of randomized clinical trials. Am. J. Alzheimers Dis. Other Demen. 30 (2015), 178–182, 10.1177/1533317514542644.
117. Jaturapatporn, D., Isaac, M.G.E.K.N., McCleery, J., Tabet, N., Aspirin, steroidal and non-steroidal anti-inflammatory drugs for the treatment of Alzheimer's disease. Cochrane Database Syst. Rev., 2012, CD006378, 10.1002/14651858.CD006378.pub2.
118. Breitner, J.C., Baker, L.D., Montine, T.J., Meinert, C.L., Lyketsos, C.G., Ashe, K.H., Brandt, J., Craft, S., Evans, D.E., Green, R.C., Ismail, M.S., Martin, B.K., Mullan, M.J., Sabbagh, M., Tariot, P.N., ADAPT research group, extended results of the Alzheimer's disease anti-inflammatory prevention trial. Alzheimers Dement. J. Alzheimers Assoc. 7 (2011), 402–411, 10.1016/j.jalz.2010.12.014.
119. Hollingworth, P., Harold, D., Sims, R., Gerrish, A., Lambert, J.-C., et al. Common variants at ABCA7, MS EPHA1, CD33 and CD2AP are associated with Alzheimer's disease. Nat. Genet. 43 (2011), 429–435, 10.1038/ng.803.
120. Naj, A.C., Jun, G., Beecham, G.W., Wang, L.-S., Vardarajan, B.N., et al. Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's disease. Nat. Genet. 43 (2011), 436–441, 10.1038/ng.801.
121. Roussos, P., Katsel, P., Fam, P., Tan, W., Purohit, D.P., Haroutunian, V., The triggering receptor expressed on myeloid cells 2 (TREM2) is associated with enhanced inflammation, neuropathological lesions and increased risk for Alzheimer's dementia, Alzheimers Dement. J. Alzheimers Assoc. 11 (2015), 1163–1170, 10.1016/j.jalz.2014.10.013.
122. Janelsins, M.C., Mastrangelo, M.A., Oddo, S., LaFerla, F.M., Federoff, H.J., Bowers, W.J., Early correlation of microglial activation with enhanced tumor necrosis factor-alpha and monocyte chemoattractant protein-1 expression specifically within the entorhinal cortex of triple transgenic Alzheimer's disease mice. J. Neuroinflammation, 2, 2005, 23, 10.1186/1742-2094-2-23.
123. McAlpine, F.E., Lee, J.-K., Harms, A.S., Ruhn, K.A., Blurton-Jones, M., Hong, J., Das, P., Golde, T.E., LaFerla, F.M., Oddo, S., Blesch, A., Tansey, M.G., Inhibition of soluble TNF signaling in a mouse model of Alzheimer's disease prevents pre-plaque amyloid-associated neuropathology. Neurobiol. Dis. 34 (2009), 163–177.
124. Cavanagh, C., Tse, Y.C., Nguyen, H.-B., Krantic, S., Breitner, J.C.S., Quirion, R., Wong, T.P., Inhibiting tumor necrosis factor-α before amyloidosis prevents synaptic deficits in an Alzheimer's disease model. Neurobiol. Aging 47 (2016), 41–49, 10.1016/j.neurobiolaging.2016.07.009.
125. Hanzel, C.E., Pichet-Binette, A., Pimentel, L.S.B., Iulita, M.F., Allard, S., Ducatenzeiler, A., Do Carmo, S., Cuello, A.C., Neuronal driven pre-plaque inflammation in a transgenic rat model of Alzheimer's disease. Neurobiol. Aging 35 (2014), 2249–2262, 10.1016/j.neurobiolaging.2014.03.026.
126. Pimentel, L.S., Allard, S., Do Carmo, S., Weinreb, O., Danik, M., Hanzel, C.E., Youdim, M.B., Cuello, A.C., The multi-target drug M30 shows pro-cognitive and anti-inflammatory effects in a rat model of Alzheimer's disease. J. Alzheimers Dis. JAD 47 (2015), 373–383, 10.3233/JAD-143126.
127. Ferretti, M.T., Allard, S., Partridge, V., Ducatenzeiler, A., Cuello, A.C., Minocycline corrects early, pre-plaque neuroinflammation and inhibits BACE-1 in a transgenic model of Alzheimer's disease-like amyloid pathology. J. Neuroinflammation, 9, 2012, 62, 10.1186/1742-2094-9-62.
128. Bruno, M.A., Leon, W.C., Fragoso, G., Mushynski, W.E., Almazan, G., Cuello, A.C., Amyloid beta-induced nerve growth factor dysmetabolism in Alzheimer disease. J. Neuropathol. Exp. Neurol. 68 (2009), 857–869, 10.1097/NEN.0b013e3181aed9e6.
129. Jack, C.R., Knopman, D.S., Jagust, W.J., Petersen, R.C., Weiner, M.W., Aisen, P.S., Shaw, L.M., Vemuri, P., Wiste, H.J., Weigand, S.D., Lesnick, T.G., Pankratz, V.S., Donohue, M.C., Trojanowski, J.Q., Tracking pathophysiological processes in Alzheimer's disease: an updated hypothetical model of dynamic biomarkers. Lancet Neurol. 12 (2013), 207–216, 10.1016/S1474-4422(12)70291-0.
130. McDade, E., Bateman, R.J., Stop Alzheimer's before it starts. Nature 547 (2017), 153–155, 10.1038/547153a.
131. Rodriguez-Vieitez, E., Saint-Aubert, L., Carter, S.F., Almkvist, O., Farid, K., Schöll, M., Chiotis, K., Thordardottir, S., Graff, C., Wall, A., Långström, B., Nordberg, A., Diverging longitudinal changes in astrocytosis and amyloid PET in autosomal dominant Alzheimer's disease. Brain J. Neurol. 139 (2016), 922–936, 10.1093/brain/awv404.
132. Walker, K.A., Hoogeveen, R.C., Folsom, A.R., Ballantyne, C.M., Knopman, D.S., Windham, B.G., Jack, C.R., Gottesman, R.F., Midlife systemic inflammatory markers are associated with late-life brain volume: the ARIC study. Neurology 89 (2017), 2262–2270, 10.1212/WNL.0000000000004688.
133. Dinarello, C.A., Anti-inflammatory agents: present and future. Cell 140 (2010), 935–950, 10.1016/j.cell.2010.02.043.
134. Tobinick, E., Gross, H., Weinberger, A., Cohen, H., TNF-alpha modulation for treatment of Alzheimer's disease: a 6-month pilot study. MedGenMed Medscape Gen. Med., 8, 2006, 25.
135. Butchart, J., Brook, L., Hopkins, V., Teeling, J., Püntener, U., Culliford, D., Sharples, R., Sharif, S., McFarlane, B., Raybould, R., Thomas, R., Passmore, P., Perry, V.H., Holmes, C., Etanercept in Alzheimer disease: a randomized, placebo-controlled, double-blind, phase 2 trial. Neurology 84 (2015), 2161–2168, 10.1212/WNL.0000000000001617.
136. Shi, J.-Q., Wang, B.-R., Jiang, W.-W., Chen, J., Zhu, Y.-W., Zhong, L.-L., Zhang, Y.-D., Xu, J., Cognitive improvement with intrathecal administration of infliximab in a woman with Alzheimer's disease. J. Am. Geriatr. Soc. 59 (2011), 1142–1144, 10.1111/j.1532-5415.2011.03445.x.
137. Pascual, G., Fong, A.L., Ogawa, S., Gamliel, A., Li, A.C., Perissi, V., Rose, D.W., Willson, T.M., Rosenfeld, M.G., Glass, C.K., A SUMOylation-dependent pathway mediates transrepression of inflammatory response genes by PPAR-gamma. Nature 437 (2005), 759–763, 10.1038/nature03988.
138. Landreth, G., Jiang, Q., Mandrekar, S., Heneka, M., PPARgamma agonists as therapeutics for the treatment of Alzheimer's disease. Neurother. J. Am. Soc. Exp. Neurother. 5 (2008), 481–489, 10.1016/j.nurt.2008.05.003.
139. Watson, G.S., Cholerton, B.A., Reger, M.A., Baker, L.D., Plymate, S.R., Asthana, S., Fishel, M.A., Kulstad, J.J., Green, P.S., Cook, D.G., Kahn, S.E., Keeling, M.L., Craft, S., Preserved cognition in patients with early Alzheimer disease and amnestic mild cognitive impairment during treatment with rosiglitazone: a preliminary study. Am. J. Geriatr. Psychiatry 13 (2005), 950–958, 10.1176/appi.ajgp.13.11.950.
140. Risner, M.E., Saunders, A.M., Altman, J.F.B., Ormandy, G.C., Craft, S., Foley, I.M., Zvartau-Hind, M.E., Hosford, D.A., Roses, A.D., Rosiglitazone in Alzheimer's Disease Study Group, Efficacy of rosiglitazone in a genetically defined population with mild-to-moderate Alzheimer's disease. Pharmacogenomics J. 6 (2006), 246–254, 10.1038/sj.tpj.6500369.
141. Lachmann, H.J., Kone-Paut, I., Kuemmerle-Deschner, J.B., Leslie, K.S., Hachulla, E., Quartier, P., Gitton, X., Widmer, A., Patel, N., Hawkins, P.N., Canakinumab in CAPS Study Group, Use of canakinumab in the cryopyrin-associated periodic syndrome. N. Engl. J. Med. 360 (2009), 2416–2425, 10.1056/NEJMoa0810787.
142. Dhimolea, E., Canakinumab. MAbs 2 (2010), 3–13.
143. Martinon, F., Burns, K., Tschopp, J., The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta. Mol. Cell. 10 (2002), 417–426.
144. de Rivero Vaccari, J.P., Dietrich, W.D., Keane, R.W., Activation and regulation of cellular inflammasomes: gaps in our knowledge for central nervous system injury. J. Cereb. Blood Flow Metab. 34 (2014), 369–375, 10.1038/jcbfm.2013.227.
145. Walsh, J.G., Muruve, D.A., Power, C., Inflammasomes in the CNS. Nat. Rev. Neurosci. 15 (2014), 84–97, 10.1038/nrn3638.
146. Latz, E., Xiao, T.S., Stutz, A., Activation and regulation of the inflammasomes. Nat. Rev. Immunol. 13 (2013), 397–411, 10.1038/nri3452.
147. Heneka, M.T., Kummer, M.P., Stutz, A., Delekate, A., Schwartz, S., Vieira-Saecker, A., Griep, A., Axt, D., Remus, A., Tzeng, T.-C., Gelpi, E., Halle, A., Korte, M., Latz, E., Golenbock, D.T., NLRP3 is activated in Alzheimer's disease and contributes to pathology in APP/PS1 mice. Nature 493 (2013), 674–678, 10.1038/nature11729.
148. Kaushal, V., Dye, R., Pakavathkumar, P., Foveau, B., Flores, J., Hyman, B., Ghetti, B., Koller, B.H., LeBlanc, A.C., Neuronal NLRP1 inflammasome activation of Caspase-1 coordinately regulates inflammatory interleukin-1-beta production and axonal degeneration-associated Caspase-6 activation. Cell Death Differ. 22 (2015), 1676–1686, 10.1038/cdd.2015.16.
149. Yin, J., Zhao, F., Chojnacki, J.E., Fulp, J., Klein, W.L., Zhang, S., Zhu, X., NLRP3 inflammasome inhibitor ameliorates amyloid pathology in a mouse model of Alzheimer's disease. Mol. Neurobiol., 2017, 10.1007/s12035-017-0467-9.
150. Daniels, M.J.D., Rivers-Auty, J., Schilling, T., Spencer, N.G., Watremez, W., Fasolino, V., Booth, S.J., White, C.S., Baldwin, A.G., Freeman, S., Wong, R., Latta, C., Yu, S., Jackson, J., Fischer, N., Koziel, V., Pillot, T., Bagnall, J., Allan, S.M., Paszek, P., Galea, J., Harte, M.K., Eder, C., Lawrence, C.B., Brough, D., Fenamate NSAIDs inhibit the NLRP3 inflammasome and protect against Alzheimer's disease in rodent models. Nat. Commun., 7, 2016, 12504, 10.1038/ncomms12504.
151. Bradshaw, E.M., Chibnik, L.B., Keenan, B.T., Ottoboni, L., Raj, T., Tang, A., Rosenkrantz, L.L., Imboywa, S., Lee, M., Von Korff, A., Alzheimer Disease Neuroimaging Initiative, Morris, M.C., Evans, D.A., Johnson, K., Sperling, R.A., Schneider, J.A., Bennett, D.A., De Jager, P.L., CD33 Alzheimer's disease locus: altered monocyte function and amyloid biology. Nat. Neurosci. 16 (2013), 848–850, 10.1038/nn.3435.
152. Griciuc, A., Serrano-Pozo, A., Parrado, A.R., Lesinski, A.N., Asselin, C.N., Mullin, K., Hooli, B., Choi, S.H., Hyman, B.T., Tanzi, R.E., Alzheimer's disease risk gene CD33 inhibits microglial uptake of amyloid beta. Neuron 78 (2013), 631–643, 10.1016/j.neuron.2013.04.014.
153. Kleinberger, G., Yamanishi, Y., Suárez-Calvet, M., Czirr, E., Lohmann, E., Cuyvers, E., Struyfs, H., Pettkus, N., Wenninger-Weinzierl, A., Mazaheri, F., Tahirovic, S., Lleó, A., Alcolea, D., Fortea, J., Willem, M., Lammich, S., Molinuevo, J.L., Sánchez-Valle, R., Antonell, A., Ramirez, A., Heneka, M.T., Sleegers, K., van der Zee, J., Martin, J.-J., Engelborghs, S., Demirtas-Tatlidede, A., Zetterberg, H., Van Broeckhoven, C., Gurvit, H., Wyss-Coray, T., Hardy, J., Colonna, M., Haass, C., TREM2 mutations implicated in neurodegeneration impair cell surface transport and phagocytosis. Sci. Transl. Med., 6, 2014, 10.1126/scitranslmed.3009093 243ra86.
154. Wang, Y., Cella, M., Mallinson, K., Ulrich, J.D., Young, K.L., Robinette, M.L., Gilfillan, S., Krishnan, G.M., Sudhakar, S., Zinselmeyer, B.H., Holtzman, D.M., Cirrito, J.R., Colonna, M., TREM2 lipid sensing sustains the microglial response in an Alzheimer's disease model. Cell 160 (2015), 1061–1071, 10.1016/j.cell.2015.01.049.
155. Laing, A.A., Harrison, C.J., Gibson, B.E.S., Keeshan, K., Unlocking the potential of anti-CD33 therapy in adult and childhood acute myeloid leukemia. Exp. Hematol. 54 (2017), 40–50, 10.1016/j.exphem.2017.06.007.
156. Dubois, B., Feldman, H.H., Jacova, C., Hampel, H., Molinuevo, J.L., Blennow, K., DeKosky, S.T., Gauthier, S., Selkoe, D., Bateman, R., Cappa, S., Crutch, S., Engelborghs, S., Frisoni, G.B., Fox, N.C., Galasko, D., Habert, M.-O., Jicha, G.A., Nordberg, A., Pasquier, F., Rabinovici, G., Robert, P., Rowe, C., Salloway, S., Sarazin, M., Epelbaum, S., de Souza, L.C., Vellas, B., Visser, P.J., Schneider, L., Stern, Y., Scheltens, P., Cummings, J.L., Advancing research diagnostic criteria for Alzheimer's disease: the IWG-2 criteria. Lancet Neurol. 13 (2014), 614–629, 10.1016/S1474-4422(14)70090-0.
157. Wang, J., Gu, B.J., Masters, C.L., Wang, Y.-J., A systemic view of Alzheimer disease – insights from amyloid-β metabolism beyond the brain. Nat. Rev. Neurol. 13 (2017), 612–623, 10.1038/nrneurol.2017.111.
158. Dubois, B., Hampel, H., Feldman, H.H., Scheltens, P., Aisen, P., Andrieu, S., Bakardjian, H., Benali, H., Bertram, L., Blennow, K., Broich, K., Cavedo, E., Crutch, S., Dartigues, J.-F., Duyckaerts, C., Epelbaum, S., Frisoni, G.B., Gauthier, S., Genthon, R., Gouw, A.A., Habert, M.-O., Holtzman, D.M., Kivipelto, M., Lista, S., Molinuevo, J.-L., O'Bryant, S.E., Rabinovici, G.D., Rowe, C., Salloway, S., Schneider, L.S., Sperling, R., Teichmann, M., Carrillo, M.C., Cummings, J., Jack, C.R., Proceedings of the Meeting of the International Working Group (IWG) and the American Alzheimer's Association on The Preclinical State of AD; July 23, 2015; Washington DC, USA, Preclinical Alzheimer's disease: Definition, natural history, and diagnostic criteria, Alzheimers Dement. J. Alzheimers Assoc. 12 (2016), 292–323, 10.1016/j.jalz.2016.02.002.
159. Wang, Y.-J., Alzheimer disease: lessons from immunotherapy for Alzheimer disease. Nat. Rev. Neurol. 10 (2014), 188–189, 10.1038/nrneurol.2014.44.
160. Jan, A., Adolfsson, O., Allaman, I., Buccarello, A.-L., Magistretti, P.J., Pfeifer, A., Muhs, A., Lashuel, H.A., Abeta42 neurotoxicity is mediated by ongoing nucleated polymerization process rather than by discrete Abeta42 species. J. Biol. Chem. 286 (2011), 8585–8596, 10.1074/jbc.M110.172411.
161. Anand, R., Gill, K.D., Mahdi, A.A., Therapeutics of Alzheimer's disease: past, present and future. Neuropharmacology 76:Pt A (2014), 27–50, 10.1016/j.neuropharm.2013.07.004.
162. Selkoe, D.J., Hardy, J., The amyloid hypothesis of Alzheimer's disease at 25 years. EMBO Mol. Med. 8 (2016), 595–608, 10.15252/emmm.201606210.
163. Beel, A.J., Sanders, C.R., Substrate specificity of gamma-secretase and other intramembrane proteases. Cell. Mol. Life Sci. CMLS 65 (2008), 1311–1334, 10.1007/s00018-008-7462-2.
164. Abramov, E., Dolev, I., Fogel, H., Ciccotosto, G.D., Ruff, E., Slutsky, I., Amyloid-beta as a positive endogenous regulator of release probability at hippocampal synapses. Nat. Neurosci. 12 (2009), 1567–1576, 10.1038/nn.2433.
165. Zimbone, S., Monaco, I., Gianì, F., Pandini, G., Copani, A.G., Giuffrida, M.L., Rizzarelli, E., Amyloid Beta monomers regulate cyclic adenosine monophosphate response element binding protein functions by activating type-1 insulin-like growth factor receptors in neuronal cells. Aging Cell, 17, 2018, 10.1111/acel.12684.
166. Parsons, C.G., Rammes, G., Preclinical to phase II amyloid beta (Aβ) peptide modulators under investigation for Alzheimer's disease. Expert Opin. Investig. Drugs 26 (2017), 579–592, 10.1080/13543784.2017.1313832.
167. Nalivaeva, N.N., Beckett, C., Belyaev, N.D., Turner, A.J., Are amyloid-degrading enzymes viable therapeutic targets in Alzheimer's disease?. J. Neurochem. 120:Suppl. 1 (2012), 167–185, 10.1111/j.1471-4159.2011.07510.x.
168. Cabrol, C., Huzarska, M.A., Dinolfo, C., Rodriguez, M.C., Reinstatler, L., Ni, J., Yeh, L.-A., Cuny, G.D., Stein, R.L., Selkoe, D.J., Leissring, M.A., Small-molecule activators of insulin-degrading enzyme discovered through high-throughput compound screening. PLoS One, 4, 2009, e5274, 10.1371/journal.pone.0005274.
169. Martel, C.L., Mackic, J.B., Matsubara, E., Governale, S., Miguel, C., Miao, W., McComb, J.G., Frangione, B., Ghiso, J., Zlokovic, B.V., Isoform-specific effects of apolipoproteins E2 E3, and E4 on cerebral capillary sequestration and blood-brain barrier transport of circulating Alzheimer's amyloid beta. J. Neurochem. 69 (1997), 1995–2004.
170. Zlokovic, B.V., Clearing amyloid through the blood-brain barrier. J. Neurochem. 89 (2004), 807–811, 10.1111/j.1471-4159.2004.02385.x.
171. Erickson, M.A., Banks, W.A., Blood-brain barrier dysfunction as a cause and consequence of Alzheimer's disease. J. Cereb. Blood Flow Metab. 33 (2013), 1500–1513, 10.1038/jcbfm.2013.135.
172. Golde, T.E., Das, P., Levites, Y., Quantitative and mechanistic studies of Abeta immunotherapy. CNS Neurol. Disord. Drug Targets 8 (2009), 31–49.
173. Winblad, B., Andreasen, N., Minthon, L., Floesser, A., Imbert, G., Dumortier, T., Maguire, R.P., Blennow, K., Lundmark, J., Staufenbiel, M., Orgogozo, J.-M., Graf, A., Safety, tolerability, and antibody response of active Aβ immunotherapy with CAD106 in patients with Alzheimer's disease: randomised, double-blind, placebo-controlled, first-in-human study. Lancet Neurol. 11 (2012), 597–604, 10.1016/S1474-4422(12)70140-0.
174. Loeffler, D.A., Should development of Alzheimer's disease-specific intravenous immunoglobulin be considered?. J. Neuroinflammation, 11, 2014, 198, 10.1186/s12974-014-0198-z.
175. Golde, T.E., Open questions for Alzheimer's disease immunotherapy. Alzheimers Res. Ther., 6, 2014, 3, 10.1186/alzrt233.
176. Corbyn, Z., New set of Alzheimer's trials focus on prevention. Lancet Lond. Engl. 381 (2013), 614–615.
177. Holtzman, D.M., Carrillo, M.C., Hendrix, J.A., Bain, L.J., Catafau, A.M., Gault, L.M., Goedert, M., Mandelkow, E., Mandelkow, E.-M., Miller, D.S., Ostrowitzki, S., Polydoro, M., Smith, S., Wittmann, M., Hutton, M., Tau from research to clinical development. Alzheimers Dement. J. Alzheimers Assoc. 12 (2016), 1033–1039, 10.1016/j.jalz.2016.03.018.
178. Ballatore, C., Lee, V.M.-Y., Trojanowski, J.Q., Tau-mediated neurodegeneration in Alzheimer's disease and related disorders. Nat. Rev. Neurosci. 8 (2007), 663–672, 10.1038/nrn2194.
179. Khanna, M.R., Kovalevich, J., Lee, V.M.-Y., Trojanowski, J.Q., Brunden, K.R., Therapeutic strategies for the treatment of tauopathies: hopes and challenges. Alzheimers Dement. J. Alzheimers Assoc. 12 (2016), 1051–1065, 10.1016/j.jalz.2016.06.006.
180. Lee, V.M., Daughenbaugh, R., Trojanowski, J.Q., Microtubule stabilizing drugs for the treatment of Alzheimer's disease. Neurobiol. Aging. 15:Suppl. 2 (1994), S87–89.
181. Min, S.-W., Cho, S.-H., Zhou, Y., Schroeder, S., Haroutunian, V., Seeley, W.W., Huang, E.J., Shen, Y., Masliah, E., Mukherjee, C., Meyers, D., Cole, P.A., Ott, M., Gan, L., Acetylation of tau inhibits its degradation and contributes to tauopathy. Neuron 67 (2010), 953–966, 10.1016/j.neuron.2010.08.044.
182. Rissman, R.A., Poon, W.W., Blurton-Jones, M., Oddo, S., Torp, R., Vitek, M.P., LaFerla, F.M., Rohn, T.T., Cotman, C.W., Caspase-cleavage of tau is an early event in Alzheimer disease tangle pathology. J. Clin. Invest. 114 (2004), 121–130, 10.1172/JCI20640.
183. Pedersen, J.T., Sigurdsson, E.M., Tau immunotherapy for Alzheimer's disease. Trends Mol. Med. 21 (2015), 394–402, 10.1016/j.molmed.2015.03.003.
184. Lista, S., Toschi, N., Baldacci, F., Zetterberg, H., Blennow, K., Kilimann, I., Teipel, S.J., Cavedo, E., Dos Santos, A.M., Epelbaum, S., Lamari, F., Dubois, B., Floris, R., Garaci, F., Hampel, H., Alzheimer Precision Medicine Initiative (APMI), Diagnostic accuracy of CSF neurofilament light chain protein in the biomarker-guided classification system for Alzheimer's disease. Neurochem. Int. 108 (2017), 355–360, 10.1016/j.neuint.2017.05.010.
185. Olsson, B., Lautner, R., Andreasson, U., Öhrfelt, A., Portelius, E., Bjerke, M., Hölttä, M., Rosén, C., Olsson, C., Strobel, G., Wu, E., Dakin, K., Petzold, M., Blennow, K., Zetterberg, H., CSF and blood biomarkers for the diagnosis of Alzheimer's disease: a systematic review and meta-analysis. Lancet Neurol., 2016, 10.1016/S1474-4422(16)00070-3.
186. Daniele, S., Pietrobono, D., Fusi, J., Iofrida, C., Chico, L., Petrozzi, L., Gerfo, A.L., Baldacci, F., Galetta, F., Siciliano, G., Bonuccelli, U., Santoro, G., Trincavelli, M.L., Franzoni, F., Martini, C., α-Synuclein aggregates with β-amyloid or tau in human red blood cells: correlation with antioxidant capability and physical exercise in human healthy subjects. Mol. Neurobiol., 2017, 10.1007/s12035-017-0523-5.
187. Mattsson, N., Andreasson, U., Zetterberg, H., Blennow, K., Alzheimer's disease neuroimaging initiative, association of plasma neurofilament light with neurodegeneration in patients with Alzheimer disease. JAMA Neurol. 74 (2017), 557–566, 10.1001/jamaneurol.2016.6117.
188. Mattsson, N., Zetterberg, H., Janelidze, S., Insel, P.S., Andreasson, U., Stomrud, E., Palmqvist, S., Baker, D., Tan Hehir, C.A., Jeromin, A., Hanlon, D., Song, L., Shaw, L.M., Trojanowski, J.Q., Weiner, M.W., Hansson, O., Blennow, K., ADNI investigators, plasma tau in Alzheimer disease. Neurology 87 (2016), 1827–1835, 10.1212/WNL.0000000000003246.
189. Deckers, K., Camerino, I., van Boxtel, M.P.J., Verhey, F.R.J., Irving, K., Brayne, C., Kivipelto, M., Starr, J.M., Yaffe, K., de Leeuw, P.W., Köhler, S., Dementia risk in renal dysfunction: a systematic review and meta-analysis of prospective studies. Neurology 88 (2017), 198–208, 10.1212/WNL.0000000000003482.
190. Gronewold, J., Klafki, H.-W., Baldelli, E., Kaltwasser, B., Seidel, U.K., Todica, O., Volsek, M., Haußmann, U., Wiltfang, J., Kribben, A., Bruck, H., Hermann, D.M., Factors responsible for plasma β-amyloid accumulation in chronic kidney disease. Mol. Neurobiol. 53 (2016), 3136–3145, 10.1007/s12035-015-9218-y.
191. Roher, A.E., Esh, C.L., Kokjohn, T.A., Castaño, E.M., Van Vickle, G.D., Kalback, W.M., Patton, R.L., Luehrs, D.C., Daugs, I.D., Kuo, Y.-M., Emmerling, M.R., Soares, H., Quinn, J.F., Kaye, J., Connor, D.J., Silverberg, N.B., Adler, C.H., Seward, J.D., Beach, T.G., Sabbagh, M.N., Amyloid beta peptides in human plasma and tissues and their significance for Alzheimer's disease, Alzheimers Dement. J. Alzheimers Assoc. 5 (2009), 18–29, 10.1016/j.jalz.2008.10.004.
192. Bharadwaj, P., Wijesekara, N., Liyanapathirana, M., Newsholme, P., Ittner, L., Fraser, P., Verdile, G., The link between type 2 diabetes and neurodegeneration: roles for amyloid-β, amylin, and tau proteins. J. Alzheimers Dis. JAD 59 (2017), 421–432, 10.3233/JAD-161192.
193. Giuntini, M., Baldacci, F., Del Prete, E., Bonuccelli, U., Ceravolo, R., Diabetes is associated with postural and cognitive domains in Parkinson's disease. Results from a single-center study. Parkinsonism Relat. Disord. 20 (2014), 671–672, 10.1016/j.parkreldis.2014.02.016.
194. Salvadori, E., Poggesi, A., Valenti, R., Pracucci, G., Pescini, F., Pasi, M., Nannucci, S., Marini, S., Del Bene, A., Ciolli, L., Ginestroni, A., Diciotti, S., Orlandi, G., Di Donato, I., De Stefano, N., Cosottini, M., Chiti, A., Federico, A., Dotti, M.T., Bonuccelli, U., Inzitari, D., Pantoni, L., VMCI-Tuscany Study Group, Operationalizing mild cognitive impairment criteria in small vessel disease: the VMCI-Tuscany Study, Alzheimers Dement. J. Alzheimers Assoc. 12 (2016), 407–418, 10.1016/j.jalz.2015.02.010.
195. Salvadori, E., Poggesi, A., Pracucci, G., Inzitari, D., Pantoni, L., VMCI-Tuscany Study Group, Development and psychometric properties of a neuropsychological battery for mild cognitive impairment with small vessel disease: the VMCI-Tuscany Study. J. Alzheimers Dis. JAD 43 (2015), 1313–1323, 10.3233/JAD-141449.
196. de la Monte, S.M., Insulin resistance and neurodegeneration progress towards the development of new therapeutics for Alzheimer's disease. Drugs 77 (2017), 47–65, 10.1007/s40265-016-0674-0.
197. Athauda, D., Foltynie, T., Insulin resistance and Parkinson's disease: a new target for disease modification?. Prog. Neurobiol. 145–146 (2016), 98–120, 10.1016/j.pneurobio.2016.10.001.
198. Hamed, S.A., Brain injury with diabetes mellitus: evidence, mechanisms and treatment implications. Expert Rev. Clin. Pharmacol. 10 (2017), 409–428, 10.1080/17512433.2017.1293521.
199. Wijesekara, N., Gonçalves da Silva, R.A., De Felice, F.G., Fraser, P.E., Impaired peripheral glucose homeostasis and Alzheimer's disease. Neuropharmacology, 2017, 10.1016/j.neuropharm.2017.11.027 pii: S0028-3908(17)30536-1.
200. Moreno-Gonzalez, I., Edwards Iii, G., Salvadores, N., Shahnawaz, M., Diaz-Espinoza, R., Soto, C., Molecular interaction between type 2 diabetes and Alzheimer's disease through cross-seeding of protein misfolding. Mol. Psychiatry 22 (2017), 1327–1334, 10.1038/mp.2016.230.
201. Lista, S., Khachaturian, Z.S., Rujescu, D., Garaci, F., Dubois, B., Hampel, H., Application of systems theory in longitudinal studies on the origin and progression of Alzheimer's disease. Methods Mol. Biol. Clifton NJ 1303 (2016), 49–67, 10.1007/978-1-4939-2627-5_2.
202. Soininen, H., Solomon, A., Visser, P.J., Hendrix, S.B., Blennow, K., Kivipelto, M., Hartmann, T., LipiDiDiet clinical study group, 24-month intervention with a specific multinutrient in people with prodromal Alzheimer's disease (LipiDiDiet): a randomised, double-blind, controlled trial. Lancet Neurol. 16 (2017), 965–975, 10.1016/S1474-4422(17)30332-0.
203. Anastasiou, C.A., Yannakoulia, M., Kosmidis, M.H., Dardiotis, E., Hadjigeorgiou, G.M., Sakka, P., Arampatzi, X., Bougea, A., Labropoulos, I., Scarmeas, N., Mediterranean diet and cognitive health: initial results from the Hellenic Longitudinal Investigation of Ageing and Diet. PLoS One, 12, 2017, e0182048, 10.1371/journal.pone.0182048.
204. Train the Brain Consortium, Randomized trial on the effects of a combined physical/cognitive training in aged MCI subjects: the Train the Brain study. Sci. Rep., 7, 2017, 39471, 10.1038/srep39471.
205. Baldacci, F., Lista, S., Garaci, F., Bonuccelli, U., Toschi, N., Hampel, H., Biomarker-guided classification scheme of neurodegenerative diseases. J. Sport Health Sci. 5:4 (2016), 383–387, 10.1016/j.jshs.2016.08.007.
206. Cummings, J., Lee, G., Mortsdorf, T., Ritter, A., Zhong, K., Alzheimer's disease drug development pipeline: 2017. Alzheimers Dement. N. Y. 3 (2017), 367–384, 10.1016/j.trci.2017.05.002.
207. Jellinger, K.A., Attems, J., Neuropathological evaluation of mixed dementia. J. Neurol. Sci. 257 (2007), 80–87, 10.1016/j.jns.2007.01.045.
208. Lo, A.W., Ho, C., Cummings, J., Kosik, K.S., Parallel discovery of Alzheimer's therapeutics. Sci. Transl. Med., 6, 2014, 10.1126/scitranslmed.3008228 241cm5.
209. Antoniou, M., Jorgensen, A.L., Kolamunnage-Dona, R., Biomarker-guided adaptive trial designs in phase II and phase III: a methodological review. PLoS One, 11, 2016, e0149803, 10.1371/journal.pone.0149803.
210. Hess, G.P., Fonseca, E., Scott, R., Fagerness, J., Pharmacogenomic and pharmacogenetic-guided therapy as a tool in precision medicine: current state and factors impacting acceptance by stakeholders. Genet. Res., 97, 2015, e13, 10.1017/S0016672315000099.
211. Baldacci, F., Lucchesi, C., Cafalli, M., Poletti, M., Ulivi, M., Vedovello, M., Giuntini, M., Mazzucchi, S., Del Prete, E., Vergallo, A., Nuti, A., Gori, S., Migraine features in migraineurs with and without anxiety-depression symptoms: a hospital-based study. Clin. Neurol. Neurosurg. 132 (2015), 74–78, 10.1016/j.clineuro.2015.02.017.
212. Pariser, A.R., Xu, K., Milto, J., Coté, T.R., Regulatory considerations for developing drugs for rare diseases: orphan designations and early phase clinical trials. Discov. Med. 11 (2011), 367–375.
213. Karran, E., Hardy, J., A critique of the drug discovery and phase 3 clinical programs targeting the amyloid hypothesis for Alzheimer disease. Ann. Neurol. 76 (2014), 185–205, 10.1002/ana.24188.
214. Morihara, T., Chu, T., Ubeda, O., Beech, W., Cole, G.M., Selective inhibition of abeta42 production by NSAID R-enantiomers. J. Neurochem. 83 (2002), 1009–1012.
215. Eriksen, J.L., Sagi, S.A., Smith, T.E., Weggen, S., Das, P., McLendon, D.C., Ozols, V.V., Jessing, K.W., Zavitz, K.H., Koo, E.H., Golde, T.E., NSAIDs and enantiomers of flurbiprofen target gamma-secretase and lower Abeta 42 in vivo. J. Clin. Invest. 112 (2003), 440–449, 10.1172/JCI18162.
216. Galasko, D.R., Graff-Radford, N., May, S., Hendrix, S., Cottrell, B.A., Sagi, S.A., Mather, G., Laughlin, M., Zavitz, K.H., Swabb, E., Golde, T.E., Murphy, M.P., Koo, E.H., Safety, tolerability, pharmacokinetics, and Abeta levels after short-term administration of R-flurbiprofen in healthy elderly individuals. Alzheimer Dis. Assoc. Disord. 21 (2007), 292–299, 10.1097/WAD.0b013e31815d1048.
217. Wilcock, G.K., Black, S.E., Hendrix, S.B., Zavitz, K.H., Swabb, E.A., Laughlin, M.A., Tarenflurbil Phase II Study investigators, Efficacy and safety of tarenflurbil in mild to moderate Alzheimer's disease: a randomised phase II trial. Lancet Neurol. 7 (2008), 483–493, 10.1016/S1474-4422(08)70090-5.
218. Green, R.C., Schneider, L.S., Amato, D.A., Beelen, A.P., Wilcock, G., Swabb, E.A., Zavitz, K.H., Tarenflurbil Phase 3 Study Group, Effect of tarenflurbil on cognitive decline and activities of daily living in patients with mild Alzheimer disease: a randomized controlled trial. JAMA 302 (2009), 2557–2564, 10.1001/jama.2009.1866.
219. Li, T., Huang, Y., Jin, S., Ye, L., Rong, N., Yang, X., Ding, Y., Cheng, Z., Zhang, J., Wan, Z., Harrison, D.C., Hussain, I., Hall, A., Lee, D.H.S., Lau, L.-F., Matsuoka, Y., -secretase modulators do not induce Aβ-rebound and accumulation of β-C-terminal fragment. J. Neurochem. 121 (2012), 277–286, 10.1111/j.1471-4159.2011.07560.x.
220. Burton, C.R., Meredith, J.E., Barten, D.M., Goldstein, M.E., Krause, C.M., Kieras, C.J., Sisk, L., Iben, L.G., Polson, C., Thompson, M.W., Lin, X.-A., Corsa, J., Fiedler, T., Pierdomenico, M., Cao, Y., Roach, A.H., Cantone, J.L., Ford, M.J., Drexler, D.M., Olson, R.E., Yang, M.G., Bergstrom, C.P., McElhone, K.E., Bronson, J.J., Macor, J.E., Blat, Y., Grafstrom, R.H., Stern, A.M., Seiffert, D.A., Zaczek, R., Albright, C.F., Toyn, J.H., The amyloid-beta rise and gamma-secretase inhibitor potency depend on the level of substrate expression. J. Biol. Chem. 283 (2008), 22992–23003, 10.1074/jbc.M804175200.
221. Lanz, T.A., Karmilowicz, M.J., Wood, K.M., Pozdnyakov, N., Du, P., Piotrowski, M.A., Brown, T.M., Nolan, C.E., Richter, K.E.G., Finley, J.E., Fei, Q., Ebbinghaus, C.F., Chen, Y.L., Spracklin, D.K., Tate, B., Geoghegan, K.F., Lau, L.-F., Auperin, D.D., Schachter, J.B., Concentration-dependent modulation of amyloid-beta in vivo and in vitro using the gamma-secretase inhibitor, LY-450139. J. Pharmacol. Exp. Ther. 319 (2006), 924–933, 10.1124/jpet.106.110700.
222. Gitter, B.D., Czilli, D.L., Li, W., Dieckman, D.K., Bender, M.H., Nissen, J.S., Mabry, T.E., Yin, T., Boggs, L.N., McClure, D.B., Little, S.P., Johnstone, E.M., Audia, J.E., May, P.C., Hyslop, P.A., P 4-339 Stereoselective inhibition of amyloid beta peptide secretion by LY450139, a novel functional gamma secretase inhibitor. Neurobiol. Aging, 25, 2004, S571, 10.1016/S0197-4580(04)81897-9.
223. Boggs, L.N., Fuson, K.S., Gitter, B.D., Czilli, D.L., Hyslop, P.A., Bender, M.H., Li, W., Audia, J.E., Nissen, J.S., Mabry, T.E., Ni, B., Su, Y., May, P.C., P 1-419 In vivo characterization of LY450139, a novel, stereoselective, functional gamma-secretase inhibitor. Neurobiol. Aging., 25, 2004, S218, 10.1016/S0197-4580(04)80731-0.
224. Ness, D.K., Boggs, L.N., Hepburn, D.L., Gitter, B., Long, G.G., May, P.C., Piroozi, K.S., Schafer, K.A., Yang, Z., P 2-053 Reduced β-amyloid burden, increased C-99 concentrations and evaluation of neuropathology in the brains of PDAPP mice given LY450139 dihydrate daily by gavage for 5 months. Neurobiol. Aging. Suppl. 2 (2004), S238–S239, 10.1016/S0197-4580(04)80800-5.
225. Siemers, E.R., Dean, R.A., Friedrich, S., Ferguson-Sells, L., Gonzales, C., Farlow, M.R., May, P.C., Safety, tolerability, and effects on plasma and cerebrospinal fluid amyloid-beta after inhibition of gamma-secretase. Clin. Neuropharmacol. 30 (2007), 317–325, 10.1097/WNF.0b013e31805b7660.
226. Bateman, R.J., Munsell, L.Y., Morris, J.C., Swarm, R., Yarasheski, K.E., Holtzman, D.M., Human amyloid-beta synthesis and clearance rates as measured in cerebrospinal fluid in vivo. Nat. Med. 12 (2006), 856–861, 10.1038/nm1438.
227. Bateman, R.J., Siemers, E.R., Mawuenyega, K.G., Wen, G., Browning, K.R., Sigurdson, W.C., Yarasheski, K.E., Friedrich, S.W., Demattos, R.B., May, P.C., Paul, S.M., Holtzman, D.M., A gamma-secretase inhibitor decreases amyloid-beta production in the central nervous system. Ann. Neurol. 66 (2009), 48–54, 10.1002/ana.21623.
228. Doody, R.S., Raman, R., Farlow, M., Iwatsubo, T., Vellas, B., Joffe, S., Kieburtz, K., He, F., Sun, X., Thomas, R.G., Aisen, P.S., Alzheimer's Disease Cooperative Study Steering Committee, Siemers, E., Sethuraman, G., Mohs, R., Semagacestat Study Group, A phase 3 trial of semagacestat for treatment of Alzheimer's disease. N. Engl. J. Med. 369 (2013), 341–350, 10.1056/NEJMoa1210951.
229. De Strooper, B., Lessons from a failed γ-secretase Alzheimer trial. Cell 159 (2014), 721–726, 10.1016/j.cell.2014.10.016.
230. Henley, D.B., May, P.C., Dean, R.A., Siemers, E.R., Development of semagacestat (LY450139), a functional gamma-secretase inhibitor, for the treatment of Alzheimer's disease. Expert Opin. Pharmacother. 10 (2009), 1657–1664, 10.1517/14656560903044982.
231. Imbimbo, B.P., Ottonello, S., Frisardi, V., Solfrizzi, V., Greco, A., Seripa, D., Pilotto, A., Panza, F., Solanezumab for the treatment of mild-to-moderate Alzheimer's disease. Expert Rev. Clin. Immunol. 8 (2012), 135–149, 10.1586/eci.11.93.
232. DeMattos, R.B., Bales, K.R., Cummins, D.J., Dodart, J.C., Paul, S.M., Holtzman, D.M., Peripheral anti-A beta antibody alters CNS and plasma A beta clearance and decreases brain A beta burden in a mouse model of Alzheimer's disease. Proc. Natl. Acad. Sci. U. S. A. 98 (2001), 8850–8855, 10.1073/pnas.151261398.
233. DeMattos, R.B., Bales, K.R., Cummins, D.J., Paul, S.M., Holtzman, D.M., Brain to plasma amyloid-beta efflux: a measure of brain amyloid burden in a mouse model of Alzheimer's disease. Science 295 (2002), 2264–2267, 10.1126/science.1067568.
234. Seubert, P., Barbour, R., Khan, K., Motter, R., Tang, P., Kholodenko, D., Kling, K., Schenk, D., Johnson-Wood, K., Schroeter, S., Gill, D., Jacobsen, J.S., Pangalos, M., Basi, G., Games, D., Antibody capture of soluble Abeta does not reduce cortical Abeta amyloidosis in the PDAPP mouse. Neurodegener. Dis. 5 (2008), 65–71, 10.1159/000112834.
235. Walker, J.R., Pacoma, R., Watson, J., Ou, W., Alves, J., Mason, D.E., Peters, E.C., Urbina, H.D., Welzel, G., Althage, A., Liu, B., Tuntland, T., Jacobson, L.H., Harris, J.L., Schumacher, A.M., Enhanced proteolytic clearance of plasma Aβ by peripherally administered neprilysin does not result in reduced levels of brain Aβ in mice. J. Neurosci. 33 (2013), 2457–2464, 10.1523/JNEUROSCI.3407-12.2013.
236. Siemers, E.R., Friedrich, S., Dean, R.A., Gonzales, C.R., Farlow, M.R., Paul, S.M., Demattos, R.B., Safety and changes in plasma and cerebrospinal fluid amyloid beta after a single administration of an amyloid beta monoclonal antibody in subjects with Alzheimer disease. Clin. Neuropharmacol. 33 (2010), 67–73, 10.1097/WNF.0b013e3181cb577a.
237. Farlow, M., Arnold, S.E., van Dyck, C.H., Aisen, P.S., Snider, B.J., Porsteinsson, A.P., Friedrich, S., Dean, R.A., Gonzales, C., Sethuraman, G., DeMattos, R.B., Mohs, R., Paul, S.M., Siemers, E.R., Safety and biomarker effects of solanezumab in patients with Alzheimer's disease. Alzheimers Dement. J. Alzheimers Assoc. 8 (2012), 261–271, 10.1016/j.jalz.2011.09.224.
238. Doody, R.S., Thomas, R.G., Farlow, M., Iwatsubo, T., Vellas, B., Joffe, S., Kieburtz, K., Raman, R., Sun, X., Aisen, P.S., Siemers, E., Liu-Seifert, H., Mohs, R., Alzheimer's Disease Cooperative Study Steering Committee, Solanezumab Study Group, Phase 3 trials of solanezumab for mild-to-moderate Alzheimer's disease. N. Engl. J. Med. 370 (2014), 311–321, 10.1056/NEJMoa1312889.
239. Siemers, E.R., Sundell, K.L., Carlson, C., Case, M., Sethuraman, G., Liu-Seifert, H., Dowsett, S.A., Pontecorvo, M.J., Dean, R.A., Demattos, R., Phase 3 solanezumab trials: secondary outcomes in mild Alzheimer's disease patients. Alzheimers Dement. J. Alzheimers Assoc. 12 (2016), 110–120, 10.1016/j.jalz.2015.06.1893.
240. Palmqvist, S., Mattsson, N., Hansson, O., Alzheimer's Disease Neuroimaging Initiative, Cerebrospinal fluid analysis detects cerebral amyloid-β accumulation earlier than positron emission tomography. Brain J. Neurol. 139 (2016), 1226–1236, 10.1093/brain/aww015.
241. Medina, M., Avila, J., New perspectives on the role of tau in Alzheimer's disease. Implications for therapy, Biochem. Pharmacol. 88 (2014), 540–547, 10.1016/j.bcp.2014.01.013.
242. Mormino, E.C., Kluth, J.T., Madison, C.M., Rabinovici, G.D., Baker, S.L., Miller, B.L., Koeppe, R.A., Mathis, C.A., Weiner, M.W., Jagust, W.J., Alzheimer's Disease Neuroimaging Initiative, Episodic memory loss is related to hippocampal-mediated beta-amyloid deposition in elderly subjects. Brain J. Neurol. 132 (2009), 1310–1323, 10.1093/brain/awn320.
243. Jagust, W.J., Landau, S.M., Shaw, L.M., Trojanowski, J.Q., Koeppe, R.A., Reiman, E.M., Foster, N.L., Petersen, R.C., Weiner, M.W., Price, J.C., Mathis, C.A., Alzheimer's Disease Neuroimaging Initiative, Relationships between biomarkers in aging and dementia. Neurology 73 (2009), 1193–1199, 10.1212/WNL.0b013e3181bc010c.
244. Villemagne, V.L., Burnham, S., Bourgeat, P., Brown, B., Ellis, K.A., Salvado, O., Szoeke, C., Macaulay, S.L., Martins, R., Maruff, P., Ames, D., Rowe, C.C., Masters, C.L., Australian Imaging Biomarkers and Lifestyle (AIBL) Research Group, Amyloid β deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer's disease: a prospective cohort study. Lancet Neurol. 12 (2013), 357–367, 10.1016/S1474-4422(13)70044-9.
245. O'Bryant, S.E., Gupta, V., Henriksen, K., Edwards, M., Jeromin, A., Lista, S., Bazenet, C., Soares, H., Lovestone, S., Hampel, H., Montine, T., Blennow, K., Foroud, T., Carrillo, M., Graff-Radford, N., Laske, C., Breteler, M., Shaw, L., Trojanowski, J.Q., Schupf, N., Rissman, R.A., Fagan, A.M., Oberoi, P., Umek, R., Weiner, M.W., Grammas, P., Posner, H., Martins, R., STAR-B and BBBIG working groups, Guidelines for the standardization of preanalytic variables for blood-based biomarker studies in Alzheimer's disease research. Alzheimers Dement. J. Alzheimers Assoc. 11 (2015), 549–560, 10.1016/j.jalz.2014.08.099.
246. Lista, S., Zetterberg, H., O'Bryant, S.E., Blennow, K., Hampel, H., Evolving relevance of neuroproteomics in Alzheimer's disease. Methods Mol. Biol. Clifton NJ 2017 (1598), 101–115, 10.1007/978-1-4939-6952-4_5.
247. Neltner, J.H., Abner, E.L., Schmitt, F.A., Denison, S.K., Anderson, S., Patel, E., Nelson, P.T., Digital pathology and image analysis for robust high-throughput quantitative assessment of Alzheimer disease neuropathologic changes. J. Neuropathol. Exp. Neurol. 71 (2012), 1075–1085, 10.1097/NEN.0b013e3182768de4.
248. Dunn, W.D., Gearing, M., Park, Y., Zhang, L., Hanfelt, J., Glass, J.D., Gutman, D.A., Applicability of digital analysis and imaging technology in neuropathology assessment. Neuropathol. Off. J. Jpn. Soc. Neuropathol. 36 (2016), 270–282, 10.1111/neup.12273.
249. Słodkowska, J., García-Rojo, M., Digital pathology in personalized cancer therapy. Stud. Health Technol. Inf. 179 (2012), 143–154.
250. Mullard, A., BACE inhibitor bust in Alzheimer trial. Nat. Rev. Drug Discov., 16, 2017, 155, 10.1038/nrd.2017.43.
251. Kennedy, M.E., Stamford, A.W., Chen, X., Cox, K., Cumming, J.N., Dockendorf, M.F., Egan, M., Ereshefsky, L., Hodgson, R.A., Hyde, L.A., Jhee, S., Kleijn, H.J., Kuvelkar, R., Li, W., Mattson, B.A., Mei, H., Palcza, J., Scott, J.D., Tanen, M., Troyer, M.D., Tseng, J.L., Stone, J.A., Parker, E.M., Forman, M.S., The BACE1 inhibitor verubecestat (MK-8931) reduces CNS β-amyloid in animal models and in Alzheimer's disease patients. Sci. Transl. Med., 2016, a150, 10.1126/scitranslmed.aad9704.
252. Yan, R., Vassar, R., Targeting the β secretase BACE1 for Alzheimer's disease therapy. Lancet Neurol. 13 (2014), 319–329, 10.1016/S1474-4422(13)70276-X.
253. Kandalepas, P.C., Sadleir, K.R., Eimer, W.A., Zhao, J., Nicholson, D.A., Vassar, R., The Alzheimer's β-secretase BACE1 localizes to normal presynaptic terminals and to dystrophic presynaptic terminals surrounding amyloid plaques. Acta Neuropathol. (Berl) 126 (2013), 329–352, 10.1007/s00401-013-1152-3.
254. Endres, K., Fahrenholz, F., Lotz, J., Hiemke, C., Teipel, S., Lieb, K., Tüscher, O., Fellgiebel, A., Increased CSF APPs-α levels in patients with Alzheimer disease treated with acitretin. Neurology 83 (2014), 1930–1935, 10.1212/WNL.0000000000001017.
255. Marcade, M., Bourdin, J., Loiseau, N., Peillon, H., Rayer, A., Drouin, D., Schweighoffer, F., Désiré, L., Etazolate, a neuroprotective drug linking GABA(A) receptor pharmacology to amyloid precursor protein processing. J. Neurochem. 106 (2008), 392–404, 10.1111/j.1471-4159.2008.05396.x.
256. Vellas, B., Sol, O., Snyder, P.J., Ousset, P.-J., Haddad, R., Maurin, M., Lemarié, J.-C., Désiré, L., Pando, M.P., EHT0202/002 study group, EHT0202 in Alzheimer's disease: a 3-month randomized, placebo-controlled, double-blind study. Curr. Alzheimer Res. 8 (2011), 203–212.
257. Rogers, K., Felsenstein, K.M., Hrdlicka, L., Tu, Z., Albayya, F., Lee, W., Hopp, S., Miller, M.-J., Spaulding, D., Yang, Z., Hodgdon, H., Nolan, S., Wen, M., Costa, D., Blain, J.-F., Freeman, E., De Strooper, B., Vulsteke, V., Scrocchi, L., Zetterberg, H., Portelius, E., Hutter-Paier, B., Havas, D., Ahlijanian, M., Flood, D., Leventhal, L., Shapiro, G., Patzke, H., Chesworth, R., Koenig, G., Modulation of γ-secretase by EVP-0015962 reduces amyloid deposition and behavioral deficits in Tg2576 mice. Mol. Neurodegener., 7, 2012, 61, 10.1186/1750-1326-7-61.
258. Bulic, B., Ness, J., Hahn, S., Rennhack, A., Jumpertz, T., Weggen, S., Biology, Chemical, Molecular mechanism and clinical perspective of γ-secretase modulators in Alzheimer's disease. Curr. Neuropharmacol. 9 (2011), 598–622, 10.2174/157015911798376352.
259. Liang, S.H., Southon, A.G., Fraser, B.H., Krause-Heuer, A.M., Zhang, B., Shoup, T.M., Lewis, R., Volitakis, I., Han, Y., Greguric, I., Bush, A.I., Vasdev, N., Novel fluorinated 8-hydroxyquinoline based metal ionophores for exploring the metal hypothesis of Alzheimer's disease. ACS Med. Chem. Lett. 6 (2015), 1025–1029, 10.1021/acsmedchemlett.5b00281.
260. Levenson, J.M., Schroeter, S., Carroll, J.C., Cullen, V., Asp, E., Proschitsky, M., Chung, C.H.-Y., Gilead, S., Nadeem, M., Dodiya, H.B., Shoaga, S., Mufson, E.J., Tsubery, H., Krishnan, R., Wright, J., Solomon, B., Fisher, R., Gannon, K.S., NPT088 reduces both amyloid-β and tau pathologies in transgenic mice. Alzheimers Dement. N. Y. 2 (2016), 141–155, 10.1016/j.trci.2016.06.004.
261. Nordberg, A., Kadir, A., Andreasen, N., Almkvist, O., Wall, A., Långström, B., Zetterberg, H., Correlations between Alzheimer's disease cerebrospinal fluid biomarkers and cerebral glucose metabolism after 12 months of phenserine treatment. J. Alzheimers Dis. JAD 47 (2015), 691–704, 10.3233/JAD-132474.
262. Kim, J., Yoon, H., Horie, T., Burchett, J.M., Restivo, J.L., Rotllan, N., Ramírez, C.M., Verghese, P.B., Ihara, M., Hoe, H.-S., Esau, C., Fernández-Hernando, C., Holtzman, D.M., Cirrito, J.R., Ono, K., Kim, J., MicroRNA-33 regulates ApoE lipidation and amyloid-β metabolism in the brain. J. Neurosci. 35 (2015), 14717–14726, 10.1523/JNEUROSCI.2053-15.2015.
263. Morawski, M., Schilling, S., Kreuzberger, M., Waniek, A., Jäger, C., Koch, B., Cynis, H., Kehlen, A., Arendt, T., Hartlage-Rübsamen, M., Demuth, H.-U., Roßner, S., Glutaminyl cyclase in human cortex: correlation with (pGlu)-amyloid-β load and cognitive decline in Alzheimer's disease. J. Alzheimers Dis. JAD 39 (2014), 385–400, 10.3233/JAD-131535.
264. Hori, Y., Takeda, S., Cho, H., Wegmann, S., Shoup, T.M., Takahashi, K., Irimia, D., Elmaleh, D.R., Hyman, B.T., Hudry, E., A Food and DrugAdministration-approved asthma therapeutic agent impacts amyloid β in the brain in a transgenic model of Alzheimer disease. J. Biol. Chem. 290 (2015), 1966–1978, 10.1074/jbc.M114.586602.
265. Butler, D., Bendiske, J., Michaelis, M.L., Karanian, D.A., Bahr, B.A., Microtubule-stabilizing agent prevents protein accumulation-induced loss of synaptic markers. Eur. J. Pharmacol. 562 (2007), 20–27, 10.1016/j.ejphar.2007.01.053.
266. Davtyan, H., Bacon, A., Petrushina, I., Zagorski, K., Cribbs, D.H., Ghochikyan, A., Agadjanyan, M.G., Immunogenicity of DNA- and recombinant protein-based Alzheimer disease epitope vaccines. Hum. Vaccines Immunother. 10 (2014), 1248–1255, 10.4161/hv.27882.
267. Mandler, M., Santic, R., Gruber, P., Cinar, Y., Pichler, D., Funke, S.A., Willbold, D., Schneeberger, A., Schmidt, W., Mattner, F., Tailoring the antibody response to aggregated Aß using novel Alzheimer-vaccines. PLoS One, 10, 2015, e0115237, 10.1371/journal.pone.0115237.
268. Novak, P., Schmidt, R., Kontsekova, E., Zilka, N., Kovacech, B., Skrabana, R., Vince-Kazmerova, Z., Katina, S., Fialova, L., Prcina, M., Parrak, V., Dal-Bianco, P., Brunner, M., Staffen, W., Rainer, M., Ondrus, M., Ropele, S., Smisek, M., Sivak, R., Winblad, B., Novak, M., Safety and immunogenicity of the tau vaccine AADvac1 in patients with Alzheimer's disease: a randomised, double-blind, placebo-controlled, phase 1 trial. Lancet Neurol. 16 (2017), 123–134, 10.1016/S1474-4422(16)30331-3.
269. Muhs, A., Hickman, D.T., Pihlgren, M., Chuard, N., Giriens, V., Meerschman, C., van der Auwera, I., van Leuven, F., Sugawara, M., Weingertner, M.-C., Bechinger, B., Greferath, R., Kolonko, N., Nagel-Steger, L., Riesner, D., Brady, R.O., Pfeifer, A., Nicolau, C., Liposomal vaccines with conformation-specific amyloid peptide antigens define immune response and efficacy in APP transgenic mice. Proc. Natl. Acad. Sci. U. S. A. 104 (2007), 9810–9815, 10.1073/pnas.0703137104.
270. Theunis, C., Crespo-Biel, N., Gafner, V., Pihlgren, M., López-Deber, M.P., Reis, P., Hickman, D.T., Adolfsson, O., Chuard, N., Ndao, D.M., Borghgraef, P., Devijver, H., Van Leuven, F., Pfeifer, A., Muhs, A., Efficacy and safety of a liposome-based vaccine against protein Tau, assessed in tau.P301L mice that model tauopathy. PLoS One, 8, 2013, e72301, 10.1371/journal.pone.0072301.
271. Sevigny, J., Chiao, P., Bussière, T., Weinreb, P.H., Williams, L., Maier, M., Dunstan, R., Salloway, S., Chen, T., Ling, Y., O'Gorman, J., Qian, F., Arastu, M., Li, M., Chollate, S., Brennan, M.S., Quintero-Monzon, O., Scannevin, R.H., Arnold, H.M., Engber, T., Rhodes, K., Ferrero, J., Hang, Y., Mikulskis, A., Grimm, J., Hock, C., Nitsch, R.M., Sandrock, A., The antibody aducanumab reduces Aβ plaques in Alzheimer's disease. Nature 537 (2016), 50–56, 10.1038/nature19323.
272. Braczynski, A.K., Schulz, J.B., Bach, J.-P., Vaccination strategies in tauopathies and synucleinopathies. J. Neurochem. 143 (2017), 467–488, 10.1111/jnc.14207.
273. Cynis, H., Frost, J.L., Crehan, H., Lemere, C.A., Immunotherapy targeting pyroglutamate-3 Aβ: prospects and challenges. Mol. Neurodegener., 11, 2016, 48, 10.1186/s13024-016-0115-2.
274. Budni, J., Garcez, M.L., de Medeiros, J., Cassaro, E., Bellettini-Santos, T., Mina, F., Quevedo, J., The anti-inflammatory role of minocycline in Alzheimeŕs disease. Curr. Alzheimer Res. 13 (2016), 1319–1329.
275. Alam, J., Blackburn, K., Patrick, D., Neflamapimod: clinical phase 2b-ready oral small molecule inhibitor of p38α to reverse synaptic dysfunction in early Alzheimer's disease. J. Prev. Alzheimers Dis. 4 (2017), 273–278, 10.14283/jpad.2017.41.
276. Davidson, J.E., Lockhart, A., Amos, L., Stirnadel-Farrant, H.A., Mooser, V., Sollberger, M., Regeniter, A., Monsch, A.U., Irizarry, M.C., Plasma lipoprotein-associated phospholipase A2 activity in Alzheimer's disease, amnestic mild cognitive impairment, and cognitively healthy elderly subjects: a cross-sectional study. Alzheimers Res. Ther., 4, 2012, 51, 10.1186/alzrt154.
277. Bernier, L.-P., Ase, A.R., Boué-Grabot, É., Séguéla, P., Inhibition of P2 × 4 function by P2Y6 UDP receptors in microglia. Glia 61 (2013), 2038–2049, 10.1002/glia.22574.
278. Fernandez-Martos, C.M., Atkinson, R.A.K., Chuah, M.I., King, A.E., Vickers, J.C., Combination treatment with leptin and pioglitazone in a mouse model of Alzheimer's disease. Alzheimers Dement. N. Y. 3 (2017), 92–106, 10.1016/j.trci.2016.11.002.
279. Searcy, J.L., Phelps, J.T., Pancani, T., Kadish, I., Popovic, J., Anderson, K.L., Beckett, T.L., Murphy, M.P., Chen, K.-C., Blalock, E.M., Landfield, P.W., Porter, N.M., Thibault, O., Long-term pioglitazone treatment improves learning and attenuates pathological markers in a mouse model of Alzheimer's disease. J. Alzheimers Dis. JAD 30 (2012), 943–961, 10.3233/JAD-2012-111661.
280. Mandrekar-Colucci, S., Landreth, G.E., Nuclear receptors as therapeutic targets for Alzheimer's disease, Expert Opin. Ther. Targets 15 (2011), 1085–1097, 10.1517/14728222.2011.594043.
281. Lue, L.-F., Yan, S.D., Stern, D.M., Walker, D.G., Preventing activation of receptor for advanced glycation endproducts in Alzheimer's disease. Curr. Drug Targets CNS Neurol. Disord. 4 (2005), 249–266.
282. Bierhaus, A., Humpert, P.M., Morcos, M., Wendt, T., Chavakis, T., Arnold, B., Stern, D.M., Nawroth, P.P., Understanding RAGE, the receptor for advanced glycation end products. J. Mol. Med. Berl. Ger. 83 (2005), 876–886, 10.1007/s00109-005-0688-7.
283. Folch, J., Petrov, D., Ettcheto, M., Pedrós, I., Abad, S., Beas-Zarate, C., Lazarowski, A., Marin, M., Olloquequi, J., Auladell, C., Camins, A., Masitinib for the treatment of mild to moderate Alzheimer's disease. Expert Rev. Neurother. 15 (2015), 587–596, 10.1586/14737175.2015.1045419.
284. Bennett, J., Burns, J., Welch, P., Bothwell, R., Safety and tolerability of R(+) pramipexole in mild-to-moderate Alzheimer's disease. J. Alzheimers Dis. JAD 49 (2016), 1179–1187, 10.3233/JAD-150788.
285. Sivilia, S., Lorenzini, L., Giuliani, A., Gusciglio, M., Fernandez, M., Baldassarro, V.A., Mangano, C., Ferraro, L., Pietrini, V., Baroc, M.F., Viscomi, A.R., Ottonello, S., Villetti, G., Imbimbo, B.P., Calzà, L., Giardino, L., Multi-target action of the novel anti-Alzheimer compound CHF5074: in vivo study of long term treatment in Tg2576 mice. BMC Neurosci., 14, 2013, 44, 10.1186/1471-2202-14-44.
286. Porrini, V., Lanzillotta, A., Branca, C., Benarese, M., Parrella, E., Lorenzini, L., Calzà, L., Flaibani, R., Spano, P.F., Imbimbo, B.P., Pizzi, M., CHF5074 (CSP-1103) induces microglia alternative activation in plaque-free Tg2576 mice and primary glial cultures exposed to beta-amyloid. Neuroscience 302 (2015), 112–120, 10.1016/j.neuroscience.2014.10.029.
287. Xu, W., Yang, Y., Yuan, G., Zhu, W., Ma, D., Hu, S., Exendin-4, a glucagon-like peptide-1 receptor agonist, reduces Alzheimer disease-associated tau hyperphosphorylation in the hippocampus of rats with type 2 diabetes. J. Investig. Med. 63 (2015), 267–272, 10.1097/JIM.0000000000000129.
288. Hölscher, C., Central effects of GLP-1: new opportunities for treatments of neurodegenerative diseases. J. Endocrinol. 221 (2014), T31–T41, 10.1530/JOE-13-0221.
289. Ma, D.-L., Chen, F.-Q., Xu, W.-J., Yue, W.-Z., Yuan, G., Yang, Y., Early intervention with glucagon-like peptide 1 analog liraglutide prevents tau hyperphosphorylation in diabetic db/db mice. J. Neurochem. 135 (2015), 301–308, 10.1111/jnc.13248.
290. Shah, R.C., Matthews, D.C., Andrews, R.D., Capuano, A.W., Fleischman, D.A., VanderLugt, J.T., Colca, J.R., An evaluation of MSDC-0160, a prototype mTOT modulating insulin sensitizer, in patients with mild Alzheimer's disease. Curr. Alzheimer Res. 11 (2014), 564–573.
291. Colca, J.R., McDonald, W.G., Cavey, G.S., Cole, S.L., Holewa, D.D., Brightwell-Conrad, A.S., Wolfe, C.L., Wheeler, J.S., Coulter, K.R., Kilkuskie, P.M., Gracheva, E., Korshunova, Y., Trusgnich, M., Karr, R., Wiley, S.E., Divakaruni, A.S., Murphy, A.N., Vigueira, P.A., Finck, B.N., Kletzien, R.F., Identification of a mitochondrial target of thiazolidinedione insulin sensitizers (mTOT)–relationship to newly identified mitochondrial pyruvate carrier proteins. PLoS One, 8, 2013, e61551, 10.1371/journal.pone.0061551.
292. Tong, M., Deochand, C., Didsbury, J., de la Monte, S.M., T3D-959, A multi-Faceted disease remedial drug candidate for the treatment of Alzheimer's disease. J. Alzheimers Dis. JAD 51 (2016), 123–138, 10.3233/JAD-151013.
293. Fisher, A., Cholinergic modulation of amyloid precursor protein processing with emphasis on M1 muscarinic receptor: perspectives and challenges in treatment of Alzheimer's disease. J. Neurochem 120:Suppl. 1 (2012), 22–33, 10.1111/j.1471-4159.2011.07507.x.
294. Ortega-Roldan, J.L., Ossa, F., Schnell, J.R., Characterization of the human sigma-1 receptor chaperone domain structure and binding immunoglobulin protein (BiP) interactions. J. Biol. Chem. 288 (2013), 21448–21457, 10.1074/jbc.M113.450379.
295. Kaufman, A.C., Salazar, S.V., Haas, L.T., Yang, J., Kostylev, M.A., Jeng, A.T., Robinson, S.A., Gunther, E.C., van Dyck, C.H., Nygaard, H.B., Strittmatter, S.M., Fyn inhibition rescues established memory and synapse loss in Alzheimer mice. Ann. Neurol. 77 (2015), 953–971, 10.1002/ana.24394.
296. Smith, L.M., Zhu, R., Strittmatter, S.M., Disease-modifying benefit of Fyn blockade persists after washout in mouse Alzheimer's model. Neuropharmacology 130 (2018), 54–61, 10.1016/j.neuropharm.2017.11.042.
297. Atherton, J., Kurbatskaya, K., Bondulich, M., Croft, C.L., Garwood, C.J., Chhabra, R., Wray, S., Jeromin, A., Hanger, D.P., Noble, W., Calpain cleavage and inactivation of the sodium calcium exchanger-3 occur downstream of Aβ in Alzheimer's disease. Aging Cell 13 (2014), 49–59, 10.1111/acel.12148.
298. Morales-Corraliza, J., Berger, J.D., Mazzella, M.J., null Veeranna, Neubert, T.A., Ghiso, J., Rao, M.V., Staufenbiel, M., Nixon, R.A., Mathews, P.M., Calpastatin modulates APP processing in the brains of β-amyloid depositing but not wild-type mice. Neurobiol. Aging 33:1125 (2012), e9–18, 10.1016/j.neurobiolaging.2011.11.023.
299. Izzo, N.J., Staniszewski, A., To, L., Fa, M., Teich, A.F., Saeed, F., Wostein, H., Walko, T., Vaswani, A., Wardius, M., Syed, Z., Ravenscroft, J., Mozzoni, K., Silky, C., Rehak, C., Yurko, R., Finn, P., Look, G., Rishton, G., Safferstein, H., Miller, M., Johanson, C., Stopa, E., Windisch, M., Hutter-Paier, B., Shamloo, M., Arancio, O., LeVine, H., Catalano, S.M., Alzheimer's therapeutics targeting amyloid beta 1–42 oligomers I: Abeta 42 oligomer binding to specific neuronal receptors is displaced by drug candidates that improve cognitive deficits. PLoS One, 9, 2014, e111898, 10.1371/journal.pone.0111898.
300. Yi, B., Sahn, J.J., Ardestani, P.M., Evans, A.K., Scott, L.L., Chan, J.Z., Iyer, S., Crisp, A., Zuniga, G., Pierce, J.T., Martin, S.F., Shamloo, M., Small molecule modulator of sigma 2 receptor is neuroprotective and reduces cognitive deficits and neuroinflammation in experimental models of Alzheimer's disease. J. Neurochem. 140 (2017), 561–575, 10.1111/jnc.13917.
301. Gray, S.G., Epigenetic treatment of neurological disease. Epigenomics 3 (2011), 431–450, 10.2217/epi.11.67.
302. Yao, J., Zhao, L., Mao, Z., Chen, S., Wong, K.C., To, J., Brinton, R.D., Potentiation of brain mitochondrial function by S-equol and R/S-equol estrogen receptor β-selective phytoSERM treatments. Brain Res. 2013 (1514), 128–141, 10.1016/j.brainres.2013.02.021.
303. Morgan, T.E., Finch, C.E., Astrocytic estrogen receptors and impaired neurotrophic responses in a rat model of perimenopause. Front. Aging Neurosci., 7, 2015, 179, 10.3389/fnagi.2015.00179.
304. Simmons, D.A., Knowles, J.K., Belichenko, N.P., Banerjee, G., Finkle, C., Massa, S.M., Longo, F.M., A small molecule p75NTR ligand, LM11A-31, reverses cholinergic neurite dystrophy in Alzheimer's disease mouse models with mid- to late-stage disease progression. PLoS One, 9, 2014, e102136, 10.1371/journal.pone.0102136.
305. Irwin, R.W., Solinsky, C.M., Loya, C.M., Salituro, F.G., Rodgers, K.E., Bauer, G., Rogawski, M.A., Brinton, R.D., Allopregnanolone preclinical acute pharmacokinetic and pharmacodynamic studies to predict tolerability and efficacy for Alzheimer's disease. PLoS One, 10, 2015, e0128313, 10.1371/journal.pone.0128313.
306. Boland, K., Moschetti, V., Dansirikul, C., Pichereau, S., Gheyle, L., Runge, F., Zimdahl-Gelling, H., Sand, M., A phase I, randomized, proof-of-clinical-mechanism study assessing the pharmacokinetics and pharmacodynamics of the oral PDE9A inhibitor BI 409306 in healthy male volunteers. Hum. Psychopharmacol., 32, 2017, 10.1002/hup.2569.
307. Weinreb, O., Amit, T., Bar-Am, O., Youdim, M.B.H., Ladostigil: a novel multimodal neuroprotective drug with cholinesterase and brain-selective monoamine oxidase inhibitory activities for Alzheimer's disease treatment. Curr. Drug Targets 13 (2012), 483–494.
308. Rinne, J.O., Wesnes, K., Cummings, J.L., Hakulinen, P., Hallikainen, M., Hänninen, J., Murphy, M., Riordan, H., Scheinin, M., Soininen, H., Rouru, J., Tolerability of ORM-12741 and effects on episodic memory in patients with Alzheimeräs disease. Alzheimers Dement. N. Y. N. 3 (2017), 1–9, 10.1016/j.trci.2016.11.004.
309. de Jong, I.E.M., Mørk, A., Antagonism of the 5-HT6 receptor – Preclinical rationale for the treatment of Alzheimer's disease. Neuropharmacology 125 (2017), 50–63, 10.1016/j.neuropharm.2017.07.010.
310. Calhoun, A., Ko, J., Grossberg, G.T., Emerging chemical therapies targeting 5-hydroxytryptamine in the treatment of Alzheimer's disease. Expert Opin. Emerg. Drugs 22 (2017), 101–105, 10.1080/14728214.2017.1293651.
311. Wicke, K., Haupt, A., Bespalov, A., Investigational drugs targeting 5-HT6 receptors for the treatment of Alzheimer's disease. Expert Opin. Investig. Drugs 24 (2015), 1515–1528, 10.1517/13543784.2015.1102884.
312. Nirogi, R., Shinde, A., Kambhampati, R.S., Mohammed, A.R., Saraf, S.K., Badange, R.K., Bandyala, T.R., Bhatta, V., Bojja, K., Reballi, V., Subramanian, R., Benade, V., Palacharla, R.C., Bhyrapuneni, G., Jayarajan, P., Goyal, V., Jasti, V., Discovery and development of 1-[(2-bromophenyl)sulfonyl]-5-methoxy-3-[(4-methyl-1-piperazinyl)methyl]-1H-indole dimesylate monohydrate (SUVN-502): a novel, potent, selective and orally active serotonin 6 (5-HT6) receptor antagonist for potential treatment of Alzheimer's disease. J. Med. Chem. 60 (2017), 1843–1859, 10.1021/acs.jmedchem.6b01662.
313. Arnsten, A.F.T., Wang, M., Targeting prefrontal cortical systems for drug development: potential therapies for cognitive disorders. Annu. Rev. Pharmacol. Toxicol. 56 (2016), 339–360, 10.1146/annurev-pharmtox-010715-103617.