The airbag problem-a potential culprit for bench-to-bedside translational efforts: Relevance for Alzheimer's disease

Acta Neuropathologica Communications

Volumn 2, Issue 1, 2014, Pages

  Krstic, Dimitrije ^a   Knuesel, Irene ^a  

^a UNIVERSITY OF ZURICH   (Switzerland)

Author keywords

Acute phase reaction; Alzheimer's disease AD; Amyloid beta a ; Amyloid precursor protein APP; Neurodegeneration; Neuroinflammation; Oxidative stress; Reelin; Synaptic plasticity

Indexed keywords

EID: 85005781374     PISSN: None     EISSN: 20515960     Source Type: Journal    
DOI: 10.1186/2051-5960-1-62     Document Type: Review

References (108)

1. Hardy JA, Higgins GA: Alzheimer's disease: the amyloid cascade hypothesis. Science 1992,256(5054):184-185. 10.1126/science.1566067
2. Van Broeckhoven C, Haan J, Bakker E, Hardy JA, Van Hul W, Wehnert A, Vegter-Van der Vlis M, Roos RA: Amyloid beta protein precursor gene and hereditary cerebral hemorrhage with amyloidosis (Dutch). Science 1990,248(4959):1120-1122. 10.1126/science.1971458
3. Goate A, Chartier-Harlin MC, Mullan M, Brown J, Crawford F, Fidani L, Giuffra L, Haynes A, Irving N, James L, et al.: Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease. Nature 1991,349(6311):704-706. 10.1038/349704a0
4. St George-Hyslop P, Haines J, Rogaev E, Mortilla M, Vaula G, Pericak-Vance M, Foncin JF, Montesi M, Bruni A, Sorbi S, et al.: Genetic evidence for a novel familial Alzheimer's disease locus on chromosome 14. Nat Genet 1992,2(4):330-334. 10.1038/ng1292-330
5. Sherrington R, Rogaev EI, Liang Y, Rogaeva EA, Levesque G, Ikeda M, Chi H, Lin C, Li G, Holman K, et al.: Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease. Nature 1995,375(6534):754-760. 10.1038/375754a0
6. McGowan E, Pickford F, Kim J, Onstead L, Eriksen J, Yu C, Skipper L, Murphy MP, Beard J, Das P, et al.: Abeta42 is essential for parenchymal and vascular amyloid deposition in mice. Neuron 2005,47(2):191-199. 10.1016/j.neuron.2005.06.030
7. Kim J, Chakrabarty P, Hanna A, March A, Dickson DW, Borchelt DR, Golde T, Janus C: Normal cognition in transgenic BRI2-Abeta mice. Mol Neurodegeneration 2013,8(1):15. 10.1186/1750-1326-8-15
8. Flood DG, Reaume AG, Dorfman KS, Lin YG, Lang DM, Trusko SP, Savage MJ, Annaert WG, De Strooper B, Siman R, et al.: FAD mutant PS-1 gene-targeted mice: increased A beta 42 and A beta deposition without APP overproduction. Neurobiology of aging 2002,23(3):335-348. 10.1016/S0197-4580(01)00330-X
9. Guo Q, Wang Z, Li H, Wiese M, Zheng H: APP physiological and pathophysiological functions: insights from animal models. Cell research 2012,22(1):78-89. 10.1038/cr.2011.116
10. Haroutunian V, Zhou Y, Elder G, Li C, Lazzarini RA: Age-dependent spatial memory deficits in transgenic mice expressing the human mid-sized neurofilament gene: I. Brain Res Mol Brain Res 1996,42(1):62-70. 10.1016/S0169-328X(96)00114-3
11. Simon AM, Schiapparelli L, Salazar-Colocho P, Cuadrado-Tejedor M, Escribano L, Lopez de Maturana R, Del Rio J, Perez-Mediavilla A, Frechilla D: Overexpression of wild-type human APP in mice causes cognitive deficits and pathological features unrelated to Abeta levels. Neurobiol Dis 2009,33(3):369-378. 10.1016/j.nbd.2008.11.005
12. Schwab C, Hosokawa M, McGeer PL: Transgenic mice overexpressing amyloid beta protein are an incomplete model of Alzheimer disease. Exp Neurol 2004,188(1):52-64. 10.1016/j.expneurol.2004.03.016
13. Kohler C, Ebert U, Baumann K, Schroder H: Alzheimer's disease-like neuropathology of gene-targeted APP-SLxPS1mut mice expressing the amyloid precursor protein at endogenous levels. Neurobiol Dis 2005,20(2):528-540. 10.1016/j.nbd.2005.04.009
14. Wirths O, Bayer TA: Neuron loss in transgenic mouse models of Alzheimer's disease. Int J Alzheimer's Dis 2010, 2010: 723782.
15. Oakley H, Cole SL, Logan S, Maus E, Shao P, Craft J, Guillozet-Bongaarts A, Ohno M, Disterhoft J, Van Eldik L, et al.: Intraneuronal beta-amyloid aggregates, neurodegeneration, and neuron loss in transgenic mice with five familial Alzheimer's disease mutations: potential factors in amyloid plaque formation. J Neurosci 2006,26(40):10129-10140. 10.1523/JNEUROSCI.1202-06.2006
16. Hardy J, Selkoe DJ: The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science 2002,297(5580):353-356. 10.1126/science.1072994
17. Selkoe DJ: Resolving controversies on the path to Alzheimer's therapeutics. Nat Med 2011,17(9):1060-1065. 10.1038/nm.2460
18. Benilova I, Karran E, De Strooper B: The toxic Abeta oligomer and Alzheimer's disease: an emperor in need of clothes. Nat Neurosci 2012,15(3):349-357. 10.1038/nn.3028
19. Whitson JS, Selkoe DJ, Cotman CW: Amyloid beta protein enhances the survival of hippocampal neurons in vitro. Science 1989,243(4897):1488-1490. 10.1126/science.2928783
20. Koo EH, Park L, Selkoe DJ: Amyloid beta-protein as a substrate interacts with extracellular matrix to promote neurite outgrowth. Proc Natl Acad Sci U S A 1993,90(10):4748-4752. 10.1073/pnas.90.10.4748
21. Plant LD, Boyle JP, Smith IF, Peers C, Pearson HA: The production of amyloid beta peptide is a critical requirement for the viability of central neurons. J Neurosci 2003,23(13):5531-5535.
22. Lopez-Toledano MA, Shelanski ML: Neurogenic effect of beta-amyloid peptide in the development of neural stem cells. J Neurosci 2004,24(23):5439-5444. 10.1523/JNEUROSCI.0974-04.2004
23. Puzzo D, Privitera L, Leznik E, Fa M, Staniszewski A, Palmeri A, Arancio O: Picomolar amyloid-beta positively modulates synaptic plasticity and memory in hippocampus. J Neurosci 2008,28(53):14537-14545. 10.1523/JNEUROSCI.2692-08.2008
24. Lesne S, Ali C, Gabriel C, Croci N, MacKenzie ET, Glabe CG, Plotkine M, Marchand-Verrecchia C, Vivien D, Buisson A: NMDA receptor activation inhibits alpha-secretase and promotes neuronal amyloid-beta production. J Neurosci 2005,25(41):9367-9377. 10.1523/JNEUROSCI.0849-05.2005
25. Atwood CS, Obrenovich ME, Liu T, Chan H, Perry G, Smith MA, Martins RN: Amyloid-beta: a chameleon walking in two worlds: a review of the trophic and toxic properties of amyloid-beta. Brain Res Brain Res Rev 2003,43(1):1-16. 10.1016/S0165-0173(03)00174-7
26. Nunomura A, Perry G, Pappolla MA, Friedland RP, Hirai K, Chiba S, Smith MA: Neuronal oxidative stress precedes amyloid-beta deposition in down syndrome. J Neuropathol Exp Neurol 2000,59(11):1011-1017.
27. Nunomura A, Perry G, Aliev G, Hirai K, Takeda A, Balraj EK, Jones PK, Ghanbari H, Wataya T, Shimohama S, et al.: Oxidative damage is the earliest event in Alzheimer disease. J Neuropathol Exp Neurol 2001,60(8):759-767.
28. Pratico D, Clark CM, Liun F, Rokach J, Lee VY, Trojanowski JQ: Increase of brain oxidative stress in mild cognitive impairment: a possible predictor of Alzheimer disease. Arch Neurol 2002,59(6):972-976. 10.1001/archneur.59.6.972
29. Nunomura A, Tamaoki T, Motohashi N, Nakamura M, McKeel DW Jr, Tabaton M, Lee HG, Smith MA, Perry G, Zhu X: The earliest stage of cognitive impairment in transition from normal aging to Alzheimer disease is marked by prominent RNA oxidation in vulnerable neurons. J Neuropathol Exp Neurol 2012,71(3):233-241. 10.1097/NEN.0b013e318248e614
30. Nunomura A, Tamaoki T, Tanaka K, Motohashi N, Nakamura M, Hayashi T, Yamaguchi H, Shimohama S, Lee HG, Zhu X, et al.: Intraneuronal amyloid beta accumulation and oxidative damage to nucleic acids in Alzheimer disease. Neurobiol Dis 2010,37(3):731-737. 10.1016/j.nbd.2009.12.012
31. Kontush A, Berndt C, Weber W, Akopyan V, Arlt S, Schippling S, Beisiegel U: Amyloid-beta is an antioxidant for lipoproteins in cerebrospinal fluid and plasma. Free Radic Biol Med 2001,30(1):119-128. 10.1016/S0891-5849(00)00458-5
32. Kurnellas MP, Adams CM, Sobel RA, Steinman L, Rothbard JB: Amyloid fibrils composed of hexameric peptides attenuate neuroinflammation. Sci Transl Med 2013,5(179):179ra142.
33. Soscia SJ, Kirby JE, Washicosky KJ, Tucker SM, Ingelsson M, Hyman B, Burton MA, Goldstein LE, Duong S, Tanzi RE, et al.: The Alzheimer's disease-associated amyloid beta-protein is an antimicrobial peptide. PLoS One 2010,5(3):e9505. 10.1371/journal.pone.0009505
34. Little CS, Hammond CJ, MacIntyre A, Balin BJ, Appelt DM: Chlamydia pneumoniae induces Alzheimer-like amyloid plaques in brains of BALB/c mice. Neurobiol Aging 2004,25(4):419-429. 10.1016/S0197-4580(03)00127-1
35. Wozniak MA, Itzhaki RF, Shipley SJ, Dobson CB: Herpes simplex virus infection causes cellular beta-amyloid accumulation and secretase upregulation. Neurosci Lett 2007,429(2-3):95-100. 10.1016/j.neulet.2007.09.077
36. Zhao J, O'Connor T, Vassar R: The contribution of activated astrocytes to Abeta production: implications for Alzheimer's disease pathogenesis. J Neuroinflammation 2011, 8: 150. 10.1186/1742-2094-8-150
37. Monning U, Konig G, Banati RB, Mechler H, Czech C, Gehrmann J, Schreiter-Gasser U, Masters CL, Beyreuther K: Alzheimer beta A4-amyloid protein precursor in immunocompetent cells. J Biol Chem 1992,267(33):23950-23956.
38. Spitzer P, Herrmann M, Klafki HW, Smirnov A, Lewczuk P, Kornhuber J, Wiltfang J, Maler JM: Phagocytosis and LPS alter the maturation state of beta-amyloid precursor protein and induce different Abeta peptide release signatures in human mononuclear phagocytes. J Neuroinflammation 2010, 7: 59. 10.1186/1742-2094-7-59
39. Miklossy J: Alzheimer's disease-a neurospirochetosis: analysis of the evidence following Koch's and Hill's criteria. J Neuroinflammation 2011, 8: 90. 10.1186/1742-2094-8-90
40. Kamer AR, Craig RG, Pirraglia E, Dasanayake AP, Norman RG, Boylan RJ, Nehorayoff A, Glodzik L, Brys M, De Leon MJ: TNF-alpha and antibodies to periodontal bacteria discriminate between Alzheimer's disease patients and normal subjects. J Neuroimmunol 2009,216(1-2):92-97. 10.1016/j.jneuroim.2009.08.013
41. Calderon-Garciduenas L, Kavanaugh M, Block M, D'Angiulli A, Delgado-Chavez R, Torres-Jardon R, Gonzalez-Maciel A, Reynoso-Robles R, Osnaya N, Villarreal-Calderon R, et al.: Neuroinflammation, hyperphosphorylated tau, diffuse amyloid plaques, and down-regulation of the cellular prion protein in air pollution exposed children and young adults. J Alzheimers Dis 2012,28(1):93-107.
42. Fischer O: Miliare Nekrosen mit drusigen Wucherungen der Neurofibrillen, eine regelmässige Veränderung der Hirnrinde bei seniler Demenz. Monatsschr Psychiatr Neurol 1907, 22: 361-372. 10.1159/000211873
43. Xiao AW, He J, Wang Q, Luo Y, Sun Y, Zhou YP, Guan Y, Lucassen PJ, Dai JP: The origin and development of plaques and phosphorylated tau are associated with axonopathy in Alzheimer's disease. Neurosci Bull 2011,27(5):287-299. 10.1007/s12264-011-1736-7
44. Krstic D, Knuesel I: Deciphering the mechanism underlying late-onset Alzheimer disease. Nat Rev Neurol 2013,9(1):25-34.
45. Meyer-Luehmann M, Spires-Jones TL, Prada C, Garcia-Alloza M, De Calignon A, Rozkalne A, Koenigsknecht-Talboo J, Holtzman DM, Bacskai BJ, Hyman BT: Rapid appearance and local toxicity of amyloid-beta plaques in a mouse model of Alzheimer's disease. Nature 2008,451(7179):720-724. 10.1038/nature06616
46. Novelli A, Reilly JA, Lysko PG, Henneberry RC: Glutamate becomes neurotoxic via the N-methyl-D-aspartate receptor when intracellular energy levels are reduced. Brain research 1988,451(1-2):205-212. 10.1016/0006-8993(88)90765-2
47. Zheng H, Koo EH: The amyloid precursor protein: beyond amyloid. Mol Neurodegener 2006, 1: 5. 10.1186/1750-1326-1-5
48. Phinney AL, Calhoun ME, Wolfer DP, Lipp HP, Zheng H, Jucker M: No hippocampal neuron or synaptic bouton loss in learning-impaired aged beta-amyloid precursor protein-null mice. Neuroscience 1999,90(4):1207-1216. 10.1016/S0306-4522(98)00645-9
49. Corrigan F, Vink R, Blumbergs PC, Masters CL, Cappai R, van den Heuvel C: Characterisation of the effect of knockout of the amyloid precursor protein on outcome following mild traumatic brain injury. Brain Res 2012, 1451: 87-99.
50. Steinbach JP, Muller U, Leist M, Li ZW, Nicotera P, Aguzzi A: Hypersensitivity to seizures in beta-amyloid precursor protein deficient mice. Cell Death Differ 1998,5(10):858-866. 10.1038/sj.cdd.4400391
51. Koike MA, Lin AJ, Pham J, Nguyen E, Yeh JJ, Rahimian R, Tromberg BJ, Choi B, Green KN, LaFerla FM: APP knockout mice experience acute mortality as the result of ischemia. PLoS One 2012,7(8):e42665. 10.1371/journal.pone.0042665
52. Griffin WS, Sheng JG, Gentleman SM, Graham DI, Mrak RE, Roberts GW: Microglial interleukin-1 alpha expression in human head injury: correlations with neuronal and neuritic beta-amyloid precursor protein expression. Neurosci Lett 1994,176(2):133-136. 10.1016/0304-3940(94)90066-3
53. Murakami N, Yamaki T, Iwamoto Y, Sakakibara T, Kobori N, Fushiki S, Ueda S: Experimental brain injury induces expression of amyloid precursor protein, which may be related to neuronal loss in the hippocampus. J Neurotrauma 1998,15(11):993-1003. 10.1089/neu.1998.15.993
54. Chen XH, Siman R, Iwata A, Meaney DF, Trojanowski JQ, Smith DH: Long-term accumulation of amyloid-beta, beta-secretase, presenilin-1, and caspase-3 in damaged axons following brain trauma. Am J Pathol 2004,165(2):357-371. 10.1016/S0002-9440(10)63303-2
55. Uryu K, Chen XH, Martinez D, Browne KD, Johnson VE, Graham DI, Lee VM, Trojanowski JQ, Smith DH: Multiple proteins implicated in neurodegenerative diseases accumulate in axons after brain trauma in humans. Exp Nephrol 2007,208(2):185-192.
56. Ramirez MJ, Heslop KE, Francis PT, Rattray M: Expression of amyloid precursor protein, tau and presenilin RNAs in rat hippocampus following deafferentation lesions. Brain Res 2001,907(1-2):222-232. 10.1016/S0006-8993(01)02580-X
57. Koistinaho J, Pyykonen I, Keinanen R, Hokfelt T: Expression of beta-amyloid precursor protein mRNAs following transient focal ischaemia. Neuroreport 1996,7(15-17):2727-2731.
58. Finnie JW, Manavis J, Blumbergs PC, Kuchel TR: Axonal and neuronal amyloid precursor protein immunoreactivity in the brains of guinea pigs given tunicamycin. Vet Pathol 2000,37(6):677-680. 10.1354/vp.37-6-677
59. Whitehead SN, Hachinski VC, Cechetto DF: Interaction between a rat model of cerebral ischemia and beta-amyloid toxicity: inflammatory responses. Stroke 2005,36(1):107-112. 10.1161/01.STR.0000149627.30763.f9
60. Lee JW, Lee YK, Yuk DY, Choi DY, Ban SB, Oh KW, Hong JT: Neuro-inflammation induced by lipopolysaccharide causes cognitive impairment through enhancement of beta-amyloid generation. J Neuroinflammation 2008, 5: 37. 10.1186/1742-2094-5-37
61. Krstic D, Madhusudan A, Doehner J, Vogel P, Notter T, Imhof C, Manalastas A, Hilfiker M, Pfister S, Schwerdel C, et al.: Systemic immune challenges trigger and drive Alzheimer-like neuropathology in mice. J Neuroinflammation 2012, 9: 151. 10.1186/1742-2094-9-151
62. Sheng JG, Ito K, Skinner RD, Mrak RE, Rovnaghi CR, Van Eldik LJ, Griffin WS: In vivo and in vitro evidence supporting a role for the inflammatory cytokine interleukin-1 as a driving force in Alzheimer pathogenesis. Neurobiol Aging 1996,17(5):761-766. 10.1016/0197-4580(96)00104-2
63. Liu L, Aboud O, Jones RA, Mrak RE, Griffin WS, Barger SW: Apolipoprotein E expression is elevated by interleukin 1 and other interleukin 1-induced factors. J Neuroinflammation 2011, 8: 175. 10.1186/1742-2094-8-175
64. Barger SW, DeWall KM, Liu L, Mrak RE, Griffin WS: Relationships between expression of apolipoprotein E and beta-amyloid precursor protein are altered in proximity to Alzheimer beta-amyloid plaques: potential explanations from cell culture studies. J Neuropathol Exp Neurol 2008,67(8):773-783. 10.1097/NEN.0b013e318180ec47
65. Leyssen M, Ayaz D, Hebert SS, Reeve S, De Strooper B, Hassan BA: Amyloid precursor protein promotes post-developmental neurite arborization in the Drosophila brain. Embo J 2005,24(16):2944-2955. 10.1038/sj.emboj.7600757
66. Wang P, Yang G, Mosier DR, Chang P, Zaidi T, Gong YD, Zhao NM, Dominguez B, Lee KF, Gan WB, et al.: Defective neuromuscular synapses in mice lacking amyloid precursor protein (APP) and APP-Like protein 2. J Neurosci 2005,25(5):1219-1225. 10.1523/JNEUROSCI.4660-04.2005
67. Jonsson T, Atwal JK, Steinberg S, Snaedal J, Jonsson PV, Bjornsson S, Stefansson H, Sulem P, Gudbjartsson D, Maloney J, et al.: A mutation in APP protects against Alzheimer's disease and age-related cognitive decline. Nature 2012,488(7409):96-99. 10.1038/nature11283
68. Dawson GR, Seabrook GR, Zheng H, Smith DW, Graham S, O'Dowd G, Bowery BJ, Boyce S, Trumbauer ME, Chen HY, et al.: Age-related cognitive deficits, impaired long-term potentiation and reduction in synaptic marker density in mice lacking the beta-amyloid precursor protein. Neuroscience 1999,90(1):1-13. 10.1016/S0306-4522(98)00410-2
69. Ring S, Weyer SW, Kilian SB, Waldron E, Pietrzik CU, Filippov MA, Herms J, Buchholz C, Eckman CB, Korte M, et al.: The secreted beta-amyloid precursor protein ectodomain APPs alpha is sufficient to rescue the anatomical, behavioral, and electrophysiological abnormalities of APP-deficient mice. J Neurosci 2007,27(29):7817-7826. 10.1523/JNEUROSCI.1026-07.2007
70. Terry RD: The pathogenesis of Alzheimer disease: an alternative to the amyloid hypothesis. J Neuropathol Exp Neurol 1996,55(10):1023-1025.
71. Kamal A, Almenar-Queralt A, LeBlanc JF, Roberts EA, Goldstein LS: Kinesin-mediated axonal transport of a membrane compartment containing beta-secretase and presenilin-1 requires APP. Nature 2001,414(6864):643-648. 10.1038/414643a
72. Smith KD, Peethumnongsin E, Lin H, Zheng H, Pautler RG: Increased human wildtype tau attenuates axonal transport deficits caused by loss of APP in mouse models. Magn Reson Insights 2010, 4: 11-18.
73. Rodrigues EM, Weissmiller AM, Goldstein LS: Enhanced beta-secretase processing alters APP axonal transport and leads to axonal defects. Hum Mol Genet 2012,21(21):4587-4601. 10.1093/hmg/dds297
74. Stokin GB, Almenar-Queralt A, Gunawardena S, Rodrigues EM, Falzone T, Kim J, Lillo C, Mount SL, Roberts EA, McGowan E, et al.: Amyloid precursor protein-induced axonopathies are independent of amyloid-beta peptides. Hum Mol Genet 2008,17(22):3474-3486. 10.1093/hmg/ddn240
75. Rose SE, Chen F, Chalk JB, Zelaya FO, Strugnell WE, Benson M, Semple J, Doddrell DM: Loss of connectivity in Alzheimer's disease: an evaluation of white matter tract integrity with colour coded MR diffusion tensor imaging. J Neurol Neurosurg Psychiatry 2000,69(4):528-530. 10.1136/jnnp.69.4.528
76. Huang J, Friedland RP, Auchus AP: Diffusion tensor imaging of normal-appearing white matter in mild cognitive impairment and early Alzheimer disease: preliminary evidence of axonal degeneration in the temporal lobe. AJNR Am J Neuroradiol 2007,28(10):1943-1948. 10.3174/ajnr.A0700
77. Ringman JM, O'Neill J, Geschwind D, Medina L, Apostolova LG, Rodriguez Y, Schaffer B, Varpetian A, Tseng B, Ortiz F, et al.: Diffusion tensor imaging in preclinical and presymptomatic carriers of familial Alzheimer's disease mutations. Brain 2007,130(Pt 7):1767-1776.
78. Gili T, Cercignani M, Serra L, Perri R, Giove F, Maraviglia B, Caltagirone C, Bozzali M: Regional brain atrophy and functional disconnection across Alzheimer's disease evolution. J Neurol Neurosurg Psychiatry 2011,82(1):58-66. 10.1136/jnnp.2009.199935
79. Gold BT, Powell DK, Andersen AH, Smith CD: Alterations in multiple measures of white matter integrity in normal women at high risk for Alzheimer's disease. Neuroimage 2010,52(4):1487-1494. 10.1016/j.neuroimage.2010.05.036
80. Genin E, Hannequin D, Wallon D, Sleegers K, Hiltunen M, Combarros O, Bullido MJ, Engelborghs S, De Deyn P, Berr C, et al.: APOE and Alzheimer disease: a major gene with semi-dominant inheritance. Mol Psychiatry 2011,16(9):903-907. 10.1038/mp.2011.52
81. Aboud O, Mrak RE, Boop F, Griffin ST: Apolipoprotein epsilon 3 alleles are associated with indicators of neuronal resilience. BMC Med 2012, 10: 35. 10.1186/1741-7015-10-35
82. Mahley RW, Huang Y: Apolipoprotein e sets the stage: response to injury triggers neuropathology. Neuron 2012,76(5):871-885. 10.1016/j.neuron.2012.11.020
83. Jicha GA, Abner EL, Schmitt FA, Kryscio RJ, Riley KP, Cooper GE, Stiles N, Mendiondo MS, Smith CD, Van Eldik LJ, et al.: Preclinical AD workgroup staging: pathological correlates and potential challenges. Neurobiol Aging 2012,33(3):622 e1-622 e16.
84. Crystal H, Dickson D, Fuld P, Masur D, Scott R, Mehler M, Masdeu J, Kawas C, Aronson M, Wolfson L: Clinico-pathologic studies in dementia: nondemented subjects with pathologically confirmed Alzheimer's disease. Neurology 1988,38(11):1682-1687. 10.1212/WNL.38.11.1682
85. Snowdon DA: Aging and Alzheimer's disease: lessons from the nun study. Gerontologist 1997,37(2):150-156. 10.1093/geront/37.2.150
86. Negash S, Bennett DA, Wilson RS, Schneider JA, Arnold SE: Cognition and neuropathology in aging: multidimensional perspectives from the rush religious orders study and rush memory and aging project. Curr Alzheimer Res 2011,8(4):336-340. 10.2174/156720511795745302
87. Balasubramanian AB, Kawas CH, Peltz CB, Brookmeyer R, Corrada MM: Alzheimer disease pathology and longitudinal cognitive performance in the oldest-old with no dementia. Neurology 2012,79(9):915-921. 10.1212/WNL.0b013e318266fc77
88. Moore BD, Chakrabarty P, Levites Y, Kukar TL, Baine AM, Moroni T, Ladd TB, Das P, Dickson DW, Golde TE: Overlapping profiles of Abeta peptides in the Alzheimer's disease and pathological aging brains. Alzheimers Res Ther 2012,4(3):18. 10.1186/alzrt121
89. Maarouf CL, Daugs ID, Kokjohn TA, Walker DG, Hunter JM, Kruchowsky JC, Woltjer R, Kaye J, Castano EM, Sabbagh MN, et al.: Alzheimer's disease and non-demented high pathology control nonagenarians: comparing and contrasting the biochemistry of cognitively successful aging. PloS one 2011,6(11):e27291. 10.1371/journal.pone.0027291
90. Lue LF, Brachova L, Civin WH, Rogers J: Inflammation, A beta deposition, and neurofibrillary tangle formation as correlates of Alzheimer's disease neurodegeneration. J Neuropathol Exp Neurol 1996,55(10):1083-1088.
91. Parachikova A, Agadjanyan MG, Cribbs DH, Blurton-Jones M, Perreau V, Rogers J, Beach TG, Cotman CW: Inflammatory changes parallel the early stages of Alzheimer disease. Neurobiol Aging 2007,28(12):1821-1833. 10.1016/j.neurobiolaging.2006.08.014
92. Morimoto K, Horio J, Satoh H, Sue L, Beach T, Arita S, Tooyama I, Konishi Y: Expression profiles of cytokines in the brains of Alzheimer's disease (AD) patients compared to the brains of non-demented patients with and without increasing AD pathology. JAD 2011,25(1):59-76.
93. Franceschi C, Bonafe M, Valensin S, Olivieri F, De Luca M, Ottaviani E, De Benedictis G: Inflamm-aging: an evolutionary perspective on immunosenescence. Ann N Y Acad Sci 2000, 908: 244-254.
94. Podtelezhnikov AA, Tanis KQ, Nebozhyn M, Ray WJ, Stone DJ, Loboda AP: Molecular insights into the pathogenesis of Alzheimer's disease and its relationship to normal aging. PloS one 2011,6(12):e29610. 10.1371/journal.pone.0029610
95. Vlad SC, Miller DR, Kowall NW, Felson DT: Protective effects of NSAIDs on the development of Alzheimer disease. Neurology 2008,70(19):1672-1677. 10.1212/01.wnl.0000311269.57716.63
96. Breitner JC, Baker LD, Montine TJ, Meinert CL, Lyketsos CG, Ashe KH, Brandt J, Craft S, Evans DE, Green RC, et al.: Extended results of the Alzheimer's disease anti-inflammatory prevention trial. Alzheimers Dement 2011,7(4):402-411. 10.1016/j.jalz.2010.12.014
97. Aisen PS, Schafer KA, Grundman M, Pfeiffer E, Sano M, Davis KL, Farlow MR, Jin S, Thomas RG, Thal LJ: Effects of rofecoxib or naproxen vs placebo on Alzheimer disease progression: a randomized controlled trial. JAMA 2003,289(21):2819-2826. 10.1001/jama.289.21.2819
98. Kramer PL, Xu H, Woltjer RL, Westaway SK, Clark D, Erten-Lyons D, Kaye JA, Welsh-Bohmer KA, Troncoso JC, Markesbery WR, et al.: Alzheimer disease pathology in cognitively healthy elderly: a genome-wide study. Neurobiology of aging 2011,32(12):2113-2122. 10.1016/j.neurobiolaging.2010.01.010
99. Krstic D, Pfister S, Notter T, Knuesel I: Decisive role of Reelin signaling during early stages of Alzheimer's disease. Neuroscience 2013, 246C: 108-116.
100. Chin J, Massaro CM, Palop JJ, Thwin MT, Yu GQ, Bien-Ly N, Bender A, Mucke L: Reelin depletion in the entorhinal cortex of human amyloid precursor protein transgenic mice and humans with Alzheimer's disease. J Neurosci 2007,27(11):2727-2733. 10.1523/JNEUROSCI.3758-06.2007
101. Herring A, Donath A, Steiner KM, Widera MP, Hamzehian S, Kanakis D, Kolble K, ElAli A, Hermann DM, Paulus W, et al.: Reelin depletion is an early phenomenon of Alzheimer's pathology. JAD 2012,30(4):963-979.
102. Graff J, Rei D, Guan JS, Wang WY, Seo J, Hennig KM, Nieland TJ, Fass DM, Kao PF, Kahn M, et al.: An epigenetic blockade of cognitive functions in the neurodegenerating brain. Nature 2012,483(7388):222-226. 10.1038/nature10849
103. Sui L, Wang Y, Ju LH, Chen M: Epigenetic regulation of reelin and brain-derived neurotrophic factor genes in long-term potentiation in rat medial prefrontal cortex. Neurobiol Learn Mem 2012,97(4):425-440. 10.1016/j.nlm.2012.03.007
104. Griffin WS, Stanley LC, Ling C, White L, MacLeod V, Perrot LJ, White CL 3rd, Araoz C: Brain interleukin 1 and S-100 immunoreactivity are elevated in down syndrome and Alzheimer disease. Proc Natl Acad Sci U S A 1989,86(19):7611-7615. 10.1073/pnas.86.19.7611
105. Smith MA, Joseph JA, Perry G: Arson: tracking the culprit in Alzheimer's disease. Ann N Y Acad Sci 2000, 924: 35-38.
106. Castellani RJ, Lee HG, Siedlak SL, Nunomura A, Hayashi T, Nakamura M, Zhu X, Perry G, Smith MA: Reexamining Alzheimer's disease: evidence for a protective role for amyloid-beta protein precursor and amyloid-beta. JAD 2009,18(2):447-452.
107. Herrup K: Reimagining Alzheimer's disease-an age-based hypothesis. J Neurosci 2010,30(50):16755-16762. 10.1523/JNEUROSCI.4521-10.2010
108. Stranahan AM, Mattson MP: Recruiting adaptive cellular stress responses for successful brain ageing. Nat Rev Neurosci 2012,13(3):209-216.