Interaction between therapeutic interventions for alzheimer's disease and physiological Aβ clearance mechanisms

Frontiers in Aging Neuroscience

Volumn 7, Issue APR, 2015, Pages

  Morrone, Christopher ^a,b   Liu, Mingzhe ^a   Black, Sandra ^a,b,c   McLaurin, JoAnne ^a,b  

^a Canada   (Canada)

^b UNIVERSITY OF TORONTO   (Canada)

^c SUNNYBROOK RESEARCH INSTITUTE   (Canada)

Author keywords

Alzheimer's disease; Amyloid ; clearance; Lifestyle factors; peptide; Therapeutics; Vaccine

Indexed keywords

AMYLOID BETA PROTEIN; BETA SECRETASE INHIBITOR;

ALZHEIMER DISEASE; ARTICLE; CENTRAL NERVOUS SYSTEM; DIET; DRUG MECHANISM; EXERCISE; GROUPS BY AGE; HUMAN; IMMUNIZATION; IMMUNOTHERAPY; INTERSTITIAL FLUID; LIFESTYLE MODIFICATION; NONHUMAN; PROTEIN DEGRADATION; SLEEP; VASCULAR DISEASE;

EID: 84928781266     PISSN: None     EISSN: 16634365     Source Type: Journal    
DOI: 10.3389/fnagi.2015.00064     Document Type: Article

References (194)

1. Abbott, N. J. (2004). Evidence for bulk flow of brain interstitial fluid: significance for physiology and pathology. Neurochem. Internat. 45(4), 545-52. doi:10.1016/j.neuint.2003.11.006
2. Adolfsson, O., Pihlgren, M., Toni, N., Varisco, Y., Buccarello, A. L., Antoniello, K., et al. (2012). An effector-reduced anti-β-amyloid (Aβ) antibody with unique Aβ binding properties promotes neuroprotection and glial engulfment of Aβ. J. Neurosci. 32(28), 9677-9689.
3. Akiyama, H., Barger, S., Barnum, S., Bradt, B., Bauer, J., Cole, G.M., Cooper, N. R. et al. (2000). Inflammation and Alzheimer's disease. Neurobiol. Aging 21, 383-421.
4. Aliev, G., Ashraf, G. M., Kaminsky, Y. G., Sheikh, I. A., Sudakov, S. K., Yakhno, N. N., et al. (2013). Implication of the nutritional and nonnutritional factors in the context of preservation of cognitive performance in patients with dementia/depression and Alzheimer disease. Am. J. Alzheimer's Disease and Other Dementias 28(7), 660-70. doi:10.1177/1533317513504614
5. Arbel-Ornath, M., Hudry, E., Eikermann-Haerter, K., Hou, S., Gregory, J. L., Zhao, L., et al. (2013). Interstitial fluid drainage is impaired in ischemic stroke and Alzheimer's disease mouse models. Acta Neuropathol. 126(3), 353-64. doi:10.1007/s00401-013-1145-2.
6. Arcoverde, C., Deslandes, A., Moraes, H., Almeida, C., Araujo, N. B., Vasques, P. E., et al. (2014). Treadmill training as an augmentation treatment for Alzheimer's disease: a pilot randomized controlled study. Arq. Neuropsiquiatr. 72(3), 190-6.
7. Banks, W. A., Terrell, B., Farr, S. A., Robinson, S. M., Nonaka, N, and Morley, J. E. (2002). Passage of amyloid beta protein antibody across the blood brain barrier in a mouse model of Alzheimer's disease. Peptides 23 (12) 2223-2226.
8. Baño Otalora, B., Popovic, N., Gambini, J., Popovic, M., Viña, J., Bonet-Costa, V., et al. (2012). Circadian system functionality, hippocampal oxidative stress, and spatial memory in the APPswe/PS1dE9 transgenic model of Alzheimer disease: effects of melatonin or ramelteon. Chronobiol. Internat. 29(7), 822-34. doi:10.3109/07420528.2012.699119
9. Barbagallo, M., and Dominguez, L. J. (2014). Type 2 diabetes mellitus and Alzheimer's disease. World J. Diabetes. 5(6), 889-93. doi:10.4239/wjd.v5.i6.889
10. Barnard, N. D., Bush, A. I., Ceccarelli, A., Cooper, J., de Jager, C. a, Erickson, K. I., et al. (2014). Dietary and lifestyle guidelines for the prevention of Alzheimer's disease. Neurobiol. Aging 35 Suppl 2, S74-8. doi:10.1016/j.neurobiolaging.2014.03.033
11. Benedict, C., Byberg, L., Cedernaes, J., Hogenkamp, P. S., Giedratis, V., Kilander, L., et al. (2014). Self-reported sleep disturbance is associated with Alzheimer's disease risk in men. Alzheimer's & Dement. J. Alz. Assoc. doi:10.1016/j.jalz.2014.08.104
12. Bierhaus, A., Humpert, P. M., Morcos, M., Wendt, T., Chavakis, T., Arnold, B., et al. (2005). Understanding RAGE, the receptor for advanced glycation end products. J. Mol. Med. 83(11), 876-886.
13. Biessels, G. J., Staekenborg, S., Brunner, E., Brayne, C., and Scheltens, P. (2006). Risk of dementia in diabetes mellitus: a systematic review. Lancet Neurol. 5(1), 64-74. doi:10.1016/S1474-4422(05)70284-2
14. Britsch, S. (2007). The neuregulin-I/ErbB signaling system in development and disease (Vol. 190). Springer Science & Business Media.
15. Black,S.E., Gao, F. and Bilbao, J. (2009) Understanding White Matter Disease: Imaging-Pathological Correlations in Vascular Cognitive Impairment, Stroke. 40, no. 3 Suppl: S48-S52.
16. Britschgi, M., Olin, C. E., Johns, H. T., Takeda-Uchimura, Y., LeMieux, M. C., Rufibach, K., et al. (2009). Neuroprotective natural antibodies to assemblies of amyloidogenic peptides decrease with normal aging and advancing Alzheimer's disease. Proc. Nat.l Acad. Sci. USA 106(29), 12145-12150.
17. Carare, R. O., Bernardes-Silva, M., Newman, T. a, Page, a M., Nicoll, J. a R., Perry, V. H., and Weller, R. O. (2008). Solutes, but not cells, drain from the brain parenchyma along basement membranes of capillaries and arteries: significance for cerebral amyloid angiopathy and neuroimmunology. Neuropathol. Appl. Neurobiol. 34(2), 131-44. doi:10.1111/j.1365-2990.2007.00926.x
18. Centers for Disease Control and Prevention. Estimates of Diabetes and Its Burden in the United States. National Diabetes Statistics Report. Atlanta, GA: US Department of Health and Human Services, 2014. Available from URL: http://www.cdc.gov/diabetes/pubs/statsreport14.htm
19. Ciccone, M. M., Scicchitano, P., Zito, A., Cortese, F., Boninfante, B., Falcone, V. A., et al. (2014). Correlation between inflammatory markers of atherosclerosis and carotid intima-media thickness in Obstructive Sleep Apnea. Molecules 19(2), 1651-62. doi:10.3390/molecules19021651
20. Cipriani, G., Lucetti, C., Danti, S., and Nuti, A. (2014). Sleep disturbances and dementia. Psychogeriatrics: Off. J. Jap. Psychogeriatrics Soc. 1-10. doi:10.1111/psyg.12069
21. Coogan, A. N., Schutová, B., Husung, S., Furczyk, K., Baune, B. T., Kropp, P., et al. (2013). The circadian system in Alzheimer's disease: disturbances, mechanisms, and opportunities. Biol. Psychiat. 74(5), 333-9. doi:10.1016/j.biopsych.2012.11.021
22. Cooke, J. R., Ancoli-Israel, S., Liu, L., Loredo, J. S., Natarajan, L., Palmer, B. S., et al. (2009). Continuous positive airway pressure deepens sleep in patients with Alzheimer's disease and obstructive sleep apnea. Sleep Med. 10(10), 1101-6. doi:10.1016/j.sleep.2008.12.016
23. Cserr, H. F., Cooper, D. N., Suri, P. K., & Patlak, C. S. (1981). Efflux of radiolabeled polyethylene glycols and albumin from rat brain. Am. J. Physiol. 240(4), F319-F328.
24. Daulatzai, M. A. (2012). Quintessential risk factors: their role in promoting cognitive dysfunction and Alzheimer's disease. Neurochem. Res. 37(12), 2627-58. doi:10.1007/s11064-012-0854-6.
25. de Andrade, L. P., Gobbi, L. T. B., Coelho, F. G. M., Christofoletti, G., Costa, J. L. R., and Stella, F. (2013). Benefits of multimodal exercise intervention for postural control and frontal cognitive functions in individuals with Alzheimer's disease: a controlled trial. J. Am. Geriatrics Society 61(11), 1919-26. doi:10.1111/jgs.12531
26. Deane, R., Du Yan, S., Submamaryan, R. K., LaRue, B., Jovanovic, S., Hogg, E., et al. (2003). RAGE mediates amyloid-β peptide transport across the blood-brain barrier and accumulation in brain. Nat. Med. 9(7), 907-913.
27. Deanne, R., Wu. Z., Sagare, A., Davis, J., DuYan, S., Hamm, K. et al. (2004). LRP/amyloid-beta peptide interaction mediates differential brain efflux of Abeta isoforms. Neuron 45, 333-344.
28. Deckers, K., van Boxtel, M. P. J., Schiepers, O. J. G., de Vugt, M., Muñoz Sánchez, J. L., Anstey, K. J., et al. (2014). Target risk factors for dementia prevention: a systematic review and Delphi consensus study on the evidence from observational studies. Internat. J. Geriatrics Psychiatry doi:10.1002/gps.4245
29. DeMattos, R. B., Bales, K. R., Cummins, D. J., Dodart, J. C., Paul, S. M., and Holtzman, D. M. (2001). Peripheral anti-Aβ antibody alters CNS and plasma Aβ clearance and decreases brain Aβ burden in a mouse model of Alzheimer's disease. Proc. Nat.l Acad. Sci. USA 98(15), 8850-8855.
30. DeMattos, R. B., Bales, K. R., Cummins, D. J., Paul, S. M., and Holtzman, D. M. (2002). Brain to plasma amyloid-β efflux: a measure of brain amyloid burden in a mouse model of Alzheimer's disease. Science 295(5563), 2264-2267.
31. Di Meco, A., Joshi, Y. B., and Praticò, D. (2014). Sleep deprivation impairs memory, tau metabolism, and synaptic integrity of a mouse model of Alzheimer's disease with plaques and tangles. Neurobiol. Aging 35(8), 1813-20. doi:10.1016/j.neurobiolaging.2014.02.011
32. Donahue, J. E., Flaherty, S. L., Johanson, C. E., Duncan, J. A., Silverberg, G. D., Miller M. C., et al. (2006). RAGE, LRP-1 and amyloid-beta protein in Alzheimer's disease. Acta Neuropathol. 112, 405-415.
33. Doody, R. S., Thomas, R. G., Farlow, M., Iwatsubo, T., Vellas, B., Joffe, S., et al. (2014). Phase 3 trials of solanezumab for mild-to-moderate Alzheimer's disease. New Engl. J. Med. 370(4), 311-321.
34. Dorr, A., Sahota, B., Chinta, L. V, Brown, M. E., Lai, A. Y., Ma, K., et al. (2012). Amyloid-β-dependent compromise of microvascular structure and function in a model of Alzheimer's disease. Brain: J. Neurol. 135(Pt 10), 3039-50. doi:10.1093/brain/aws243
35. Du Yan, S., Chen, X., Fu, J., Chen, M., Zhu, H., Roher, A., et al. (1996). RAGE and amyloid-β peptide neurotoxicity in Alzheimer's disease. Nature 382(6593), 685-691.
36. Farlow, M., Arnold, S. E., van Dyck, C. H., Aisen, P. S., Snider, B. J., Porsteinsson, A. P., et al. (2012). Safety and biomarker effects of solanezumab in patients with Alzheimer's disease. Alzheimer's & Dementia 8(4), 261-271.
37. Farris, W., Mansourian, S., Chang, Y., Lindsley, L., Eckman, E.A., Frosch, M.P. et al. (2003). Insulin-degrading enzyme regulates the levels of insulin, amyloid-beta-protein, and the beta-amyloid precursor protein intracellular domain in vivo. Proc. Nat.l Acad. Sci. USA 100, 4162-4167.
38. Farris, W., Mansourian, S., Leissring, M. A., Eckman, E. A., Bertram, L., Eckman, C. B., et al. (2004). Partial Loss-of-Function Mutations in Insulin-Degrading Enzyme that Induce Diabetes also Impair Degradation of Amyloid β-Protein. Am. J. Pathol. 164(4), 1425-1434. doi:10.1016/S0002-9440(10)63229-4
39. Floyd, J. A., Medler, S. M., Ager, J. W., and Janisse, J. J. (2000). Age-Related Changes in Initiation and Maintenance of Sleep: A Meta-Analysis. Res. Nurs. Health 23, 106-117.
40. Forman, M., Tseng, J., Palcza, J., Leempoels, J., Ramael, S., Krishna, G., et al. (2012). The Novel BACE Inhibitor MK-8931 Dramatically Lowers CSF Aβ Peptides in Healthy Subjects: Results from a Rising Single Dose Study (PL02. 004) 64th American Academy of Neurology Annual Meeting; New Orleans: Neurology.
41. Frackowiak, J., Wisniewski, H. M., Wegiel, J., Merz, G. S., Iqhal, K., and Wang, K. C. (1992). Ultrastructure of the microglia that phagocytose amyloid and the microglia that produce beta-amyloid fibrils. Acta Neuropathol. 84, 225-233.
42. Frink, R. J. (2002). Inflammatory Atherosclerosis: Characteristics of the Injurious Agent. Sacramento (CA): Heart Research Foundation. ISBN-10: 0-9724816-0-5
43. Funato, H. Yoshimura, M., Yamazaki, T., Saido, T. C., Ito. Y., Yokofijita, J. et al. (1998). Astrocytes containing amyloid-b protein (Ab) positive granules are associated with Ab40-positive diffuse plaques in the aged human brain. Am. J. Pathol. 152, 983-992.
44. Gabathuler, R. (2010). Approaches to transport therapeutic drugs across the blood-brain barrier to treat brain diseases. Neurobiol. Disease 37(1), 48-57.
45. Gaberel, T., Gakuba, C., Goulay, R., Martinez De Lizarrondo, S., Hanouz, J.-L., Emery, E., et al. (2014). Impaired glymphatic perfusion after strokes revealed by contrastenhanced MRI: a new target for fibrinolysis? Stroke 45(10), 3092-6. doi:10.1161/STROKEAHA.114.006617
46. Gao F, Noor R, Keith J, Nadeau Y, Kiss A, and (2012) Black S. Relationship between collagenosis of the deep medullary veins and periventricular white matter hyperintensities on Magnetic Resonance Imaging in Alzheimer's disease: does one size fit all? Alzheimers Dement 8(4 Suppl):P297
47. Gavin, A. L., Barnes, N., Dijstelbloem, H. M., and Hogarth, P. M. (1998). Cutting edge: identification of the mouse IgG3 receptor: implications for antibody effector function at the interface between innate and adaptive immunity. J. Immunol. 160(1), 20-23.
48. Graf, A., Riviere, M. E., Caputo, A., Farlow, M. R., Marotta, G., Sanchez-Valle, R., et al. (2014). Active Aβ Immunotherapy CAD106 Phase II Dose-Adjuvant Finding Study: Safety and CNS Biomarkers. Alzheimer's & Dementia: The Journal of the Alzheimer's Association, 10(4), P274.
49. Guenette, S. Y. (2003). Astrocytes: a cellular player in Aβ clearance and degradation. Trends in Molecular Medicine 9 (7) 279-280.
50. Gustafson, D., Rothenberg, E., Blennow, K., Steen, B., and Skoog., I. (2003). An 18-year follow-up of overweight and risk of Alzheimer disease. Arch. Intern. Med. 163(13), 1524-1528. doi:10.1001/archinte.163.13.1524
51. Hadaczek, P., Yamashita, Y., Mirek, H., Tamas, L., Bohn, M. C., Noble, C., et al. (2006). The "perivascular pump" driven by arterial pulsation is a powerful mechanism for the distribution of therapeutic molecules within the brain. Mol. Ther. 14(1), 69-78. doi:10.1016/j.ymthe.2006.02.018
52. Haeberlein, S. B., Cebers, G., Höglund, K., Salter, H., Eketjäll, S., Bogstedt, A., et al. (2013). AZD3293, a potent and selective orally active, brain-permeable BACE1 inhibitor. Alzheimer's & Dementia: The Journal of the Alzheimer's Association, 9(4), P813-P813.
53. Han, S. W., Lee, S.-S., Kim, S. H., Lee, J. H., Kim, G. S., Kim, O.-J., et al. (2013). Effect of cilostazol in acute lacunar infarction based on pulsatility index of transcranial Doppler (ECLIPse): a multicenter, randomized, double-blind, placebo-controlled trial. Europ. Neurol. 69(1), 33-40. doi:10.1159/000338247
54. Hanyu, H., Hirao, K., Shimizu, S., and Sato, T. (2007). Nilvadipine prevents cognitive decline of patients with mild cognitive impairment. Internat. J. Geriatrics Psychiatry 22(April), 1264-1266. doi:10.1002/gps
55. Hardy, J., and Selkoe, D. (2002). The amyloid hypothesis of Alzheimer's disease: Progress and problems on the road to therapeutics. Science 297 (5580) 353-356.
56. Hawkes, C. A., and McLaurin, J. (2009). Selective targeting of perivascular macrophages for clearance of beta-amyloid in cerebral amyloid angiopathy. Proc. Nat.l Acad. Sci. USA 106, 1261-1266.
57. Hawkes, C. A., Deng, L.-H., Fenili, D., Nitz, M., McLaurin, J. (2011). 1-deoxy-1-fluoroscyllo-inositol increases in vivo uptake of b-amyloid by non-plaque associated microglia. Current Alzheimer Research. doi: 10.2174/1567212222726212050
58. Hawkes, C. A., Gatherer, M., Sharp, M. M., Dorr, A., Yuen, H. M., Kalaria, R., et al. (2013). Regional differences in the morphological and functional effects of aging on cerebral basement membranes and perivascular drainage of amyloid-β from the mouse brain. Aging Cell 12(2), 224-36. doi:10.1111/acel.12045
59. Hawkes, C. A., Jayakody, N., Johnston, D. a, Bechmann, I., and Carare, R. O. (2014). Failure of perivascular drainage of β-amyloid in cerebral amyloid angiopathy. Brain Pathol. 24(4), 396-403. doi:10.1111/bpa.12159
60. Hawkes, C. A., Gentleman, S. M., Nicoll, J. A., and Carare, R. O. (2015). Prenatal highfat diet alters the cerebrovasculature and clearance of β-amyloid in adult offspring. J. Pathol. doi:10.1002/path.4468
61. Hoffmann, K., Frederiksen, K. S., Sobol, N. A., Beyer, N., Vogel, A., Simonsen, A. H., et al. (2013). Preserving cognition, quality of life, physical health and functional ability in Alzheimer's disease: the effect of physical exercise (ADEX trial): rationale and design. Neuroepidemiol. 41(3-4), 198-207. doi:10.1159/000354632
62. Höglund, K., Salter, H., Zetterberg, H., Andreason, U., Olsson, T., Alexander, R., et al. (2014). Monitoring the soluble amyloid precursor protein alpha (sAPPα) and beta (sAPPβ) fragments in plasma and CSF from healthy individuals treated with BACE inhibitor AZD3293 in a multiple ascending dose study: pharmacokinetic and pharmacodynamic correlate. Alzheimer's & Dementia: The Journal of the Alzheimer's Association, 10(4), P447.
63. Ihara, M., Nishino, M., Taguchi, A., Yamamoto, Y., Hattori, Y., Saito, S., et al. (2014). Cilostazol add-on therapy in patients with mild dementia receiving donepezil: a retrospective study. PloS One 9(2), e89516. doi:10.1371/journal.pone.0089516
64. Ikeda, Y. (1999). Antiplatelet therapy using cilostazol, a specific PDE3 inhibitor. Thromb. Haemost. 82, 435-8.
65. Iliff, J. J., Wang, M., Liao, Y., Plog, B. A., Peng, W., Gundersen, G. A., et al. (2012). A Paravascular Pathway Facilitates CSF Flow Through the Brain Parenchyma and the Clearance of Interstitial Solutes, Including Amyloid β. Sci. Transl. Med. 4(147). doi:10.1126/scitranslmed.3003748.A
66. Iliff, J. J., and Nedergaard, M. (2013). Is there a cerebral lymphatic system? Stroke, 44(585). doi:10.1161/STROKEAHA.112.678698.Is
67. Iliff, J. J., Lee, H., Yu, M., Feng, T., Logan, J., Nedergaard, M., and Benveniste, H. (2013a). Brain-wide pathway for waste clearance captured by contrast-enhanced MRI. J. Clin. Invest. 123(3), 1299-309. doi:10.1172/JCI67677
68. Iliff, J. J., Wang, M., Zeppenfeld, D. M., Venkataraman, A., Plog, B. a, Liao, Y., et al. (2013b). Cerebral arterial pulsation drives paravascular CSF-interstitial fluid exchange in the murine brain. J. Neurosci. Off. J. Soc. Neurosci. 33(46), 18190-9. doi:10.1523/JNEUROSCI.1592-13.2013
69. Iwata, N., Tsubuki, S., Takaki, Y., Watanabe, K., Sekiguchi, M., Hosoki, E., et al. (2000). Identification of the major Abeta 1-42 degrading catabolic pathway in brain parenchyma: suppression leads to biochemical and pathological deposition. Nat. Med. 6, 143-150.
70. Iwata, N., Tsubuki, S., Takaki, Y., Shirotani, K., Lu, B., Gerard, N.P., et al. (2001). Metabolic regulation of brain Abeta by neprilysin. Science 292, 1550-1552.
71. Iwata, N., Takaki, Y., Fukami, S., Tsubuki, S., and Saido, T.C. (2002). Region-specific reduction of Abeta degrading endopeptidase, neprilysin, in mouse hippocampus upon aging. J. Neurosci. Res. 70, 493-500.
72. Janson, J., Laedtke, T., Parisi, J. E., Brien, P. O., Petersen, R. C., and Butler, P. C. (2004). Increased Risk of Type 2 Diabetes in Alzheimer Disease. Diabetes 53(February), 474-81.
73. Janssens, J. P., Pautex, S., Hilleret, H., and Michel, J. P. (2000). Sleep disordered breathing in the elderly. Aging 12(6), 417-29.
74. Johanson, C., Flaherty, S., Messier A., Duncan J.I., Silverberg, G. (2006). Expression of the beta-amyloid transporter, LRP-1, in aging choroid plexus: Implications for the CSFbrain system in NPH and Alzheimer's disease. Cerebrospinal Fluid Res. 3, S29
75. Kalaria R. N., and Hedera P. (1995). Differential degeneration of the cerebral microvasculature in Alzheimer's disease. Neuroreport 6:477-80.
76. Kanekiyo T., and Bu, G. (2014). The low-density lipoprotein receptor-related protein 1 and amyloid-β clearance in Alzheimer's disease. Frontiers in Aging Neuroscience 6, 93, 1-12. Doi:10.3389/fnagi.2014.00093.
77. Kang, J.-E., Lim, M. M., Bateman, R. J., Lee, J. L., Smyth, L. P., Cirrito, J. R., et al. (2009). Amyloid-β Dynamics Are Regulated by Orexin and the Sleep-Wake Cycle. Science 326(5955), 1005-7. doi:10.1126/science.1180962
78. Kivipelto, M., and Solomon, A. (2008). Alzheimer's disease - the ways of prevention. J. Nutr. Health Aging 12(1), 89S-94S.
79. Koistinaho, M., Lin, S., Wu, X., Esterman, M., Koger, D., Hanson, J., et al, (2004) Apolipoprotein E promotes astrocytes colocalization and degradation of deposited amyloid-beta peptides. Nat. Med. 10, 719-726.
80. Kress, B. T., Iliff, J. J., Xia, M., Wang, M., Wei, H., Zeppenfeld, D., et al. (2014). Impairment of paravascular clearance pathways in the aging brain. Ann. Neurol. 845- doi:10.1002/ana.24271
81. Kuhn, P. H., Koroniak, K., Hogl, S., Colombo, A., Zeitschel, U., Willem, M., et al. (2012). Secretome protein enrichment identifies physiological BACE1 protease substrates in neurons. The EMBO journal 31(14), 3157-3168.
82. Kurz, A., & Perneczky, R. (2011). Amyloid clearance as a treatment target against Alzheimer's disease. J. Alzheimer's Disease 24, 61-73.
83. Kwee, R. M., and Kwee, T. C. (2007). Virchow-Robin Spaces at MR Imaging. RadioGraphics 27(4), 1071-1086. doi:10.1148/rg.274065722
84. Lai, A.Y. and McLaurin, J. (2012) Clearance of amyloid-b by microglia and macrophages: the issue of what, when and where. Future Neurology 7(2) 1-12.
85. Lai, A. Y., Dorr, A., Thomason, L. A. M., Koletar, M. M., Sled, J. G., Stefanovic, B., and McLaurin, J. (2015). Venular degeneration leads to vascular dysfunction in a transgenic model of Alzheimer`s disease. Brain [in press 2015].
86. Lai, R., Albala, B., Kaplow, J. M., Aluri, J., Yen, M., and Satlin, A. (2012). First-inhuman study of E2609, a novel BACE1 inhibitor, demonstrates prolonged reductions in plasma beta-amyloid levels after single dosing. Alzheimer's & Dementia 8(4), P96.
87. Lee, C.Y., and Landreth, G. E. (2010). The role of microglia in amyloid clearance from the AD brain. J. Neural Transm. 117, 949-960.
88. Lee, J., Duan, W., Long, J. M., Ingram, D. K., and Mattson, M. P. (2000). Dietary restriction increases the number of newly generated neural cells, and induces BDNF expression, in the dentate gyrus of rats. J. Mol. Neurosci. 15, 99-108.
89. Lee, J., Duan, W., and Mattson, M. P. (2002). Evidence that brain-derived neurotrophic factor is required for basal neurogenesis and mediates, in part, the enhancement of neurogenesis by dietary restriction in the hippocampus of adult mice. J. Neurochem. 82(6), 1367-1375. doi:10.1046/j.1471-4159.2002.01085.x
90. Leissring, M.A., Farris, W., Chang, Y., Walsh, D. M., Wu, X., Sun, X., et al. (2003). Enhanced proteolysis of beta-amyloid in APP transgenic mice prevents plaque formation, secondary pathology, and premature death. Neuron 40, 1087-1093.
91. Liguori, C., Placidi, F., Albanese, M., Nuccetelli, M., Izzi, F., Marciani, M. G., et al. (2014). CSF beta-amyloid levels are altered in narcolepsy: a link with the inflammatory hypothesis? J. Sleep Res. 23(4), 420-4. doi:10.1111/jsr.12130.
92. Lim, Y. Y., Pietrzak, R. H., Bourgeat, P., Ames, D., Ellis, K. A., Rembach, A., et al. (2014). Relationships Between Performance on the Cogstate Brief Battery, Neurodegeneration, and Aβ Accumulation in Cognitively Normal Older Adults and Adults with MCI. Arch. Clin. Neuropsychol. doi:10.1093/arclin/acu068
93. Lin, T.-W., Shih, Y.-H., Chen, S.-J., Lien, C.-H., Chang, C.-Y., Huang, T.-Y., et al. (2014). Running exercise delays neurodegeneration in amygdala and hippocampus of Alzheimer's disease (APP/PS1) transgenic mice. Neurobiol. Learn. Mem. (December), [in press]. doi:10.1016/j.nlm.2014.12.005
94. Liu, C.-C., Kanekiyo, T., Xu, H., Bu, G. (2013). Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy. Nat Rev Neurol. 9, 106-118.
95. Liu, G., Yao, L., Liu, J., Jiang, Y., Ma, G., Chen, Z., et al. (2014). Cardiovascular disease contributes to Alzheimer's disease: evidence from large-scale genome-wide association studies. Neurobiol. Aging 35(4), 786-92. doi:10.1016/j.neurobiolaging.2013.10.084
96. Lobanova, I., and Qureshi, A. I. (2014). The association between cardiovascular risk factors and progressive hippocampus volume loss in persons with Alzheimer's disease. J. Vasc. Interv. Neurol. 7(5), 52-5.
97. Lucas, F., Fukushima, T., and Nozaki, Y. (2012). Novel BACE1 inhibitor, E2609, lowers Aβ levels in the cerebrospinal fluid and plasma in nonhuman primates. Alzheimer's & Dementia 8(4), P224.
98. Luchsinger, J. A., Tang, M. X., Shea, S., and Mayeux, R. (2002). Caloric intake and the risk of Alzheimer disease. Arch. Neurol. 59(8), 1258-63. doi:10.1001/archneur.59.8.1258
99. Maki, T., Okamoto, Y., Carare, R. O., Hase, Y., Hattori, Y., Hawkes, C. A., et al. (2014). Phosphodiesterase III inhibitor promotes drainage of cerebrovascular β-amyloid. Ann. Clin. Transl. Neurol. 1(8), 519-33. doi:10.1002/acn3.79
100. Mandrekar, S., Jiang, Q., Lee, C.Y., Koenigsknecht-Talboo, J., Holtzman, D., Landreth, G.E. (2009). Microglia mediate the clearance of soluble Abeta through fluid phase macropinocytosis. J. Neurosci. 29, 4252-4262.
101. Marques, F., Sousa, J. C., Sousa, N., Palha, J. A., (2013). Blood-brain-barriers in aging and Alzheimer's disease. Mol. Neurosci. 8(1) 38.
102. Maruszak, A., Pilarski, A., Murphy, T., Branch, N., and Thuret, S. (2014). Hippocampal neurogenesis in Alzheimer's disease: is there a role for dietary modulation? J. Alzheimer's Disease 38(1), 11-38. doi:10.3233/JAD-131004
103. Mawuenyega, K. G, Sigurdson, W., Ovod, V., Munsell, L., Kasten, T., Morris, J. C., et al. (2010) Decreased clearance of CNS beta-amyloid in Alzheimer's disease. Science 330(6012):1774.
104. Mattson, M. P. (2015). Lifelong brain health is a lifelong challenge: From evolutionary principles to empirical evidence. Ageing Res. Rev. doi:10.1016/j.arr.2014.12.011
105. McLaurin, J., Barakat, M. E., Brown, M. E., Hawkes, C. E., Lambermon, M. H. L., Phinney, A. L., et al. (2006). Cyclohexanehexol-based inhibitors of Ab-aggregation prevent and reverse Alzheimer-like features in a transgenic model of Alzheimer Disease. Nat. Med. 12, 801-808.
106. Michaud, J.-P., Bellavance, M.-A., Préfontaine, P., and Rivest, S. (2013a). Realtime in vivo imaging reveals the ability of monocytes to clear vascular amyloid beta. Cell Reports 5(3), 646-53. doi:10.1016/j.celrep.2013.10.010
107. Michaud, M., Balardy, L., Moulis, G., Gaudin, C., Peyrot, C., Vellas, B., et al. (2013b). Proinflammatory cytokines, aging, and age-related diseases. Journal of the American Medical Directors Association 14(12), 877-882.
108. Monsonego, A., Maron, R., Zota, V., Selkoe, D. J., and Weiner, H. L. (2001). Immune hyporesponsiveness to amyloid β-peptide in amyloid precursor protein transgenic mice: Implications for the pathogenesis and treatment of Alzheimer's disease. Proc. Nat.l Acad. Sci. USA 98(18), 10273-10278.
109. Monsonego, A., Zota, V., Karni, A., Krieger, J. I., Bar-Or, A., Bitan, G., et al. (2003). Increased T cell reactivity to amyloid β protein in older humans and patients with Alzheimer disease. J.Clin. Invest. 112(3), 415-422.
110. Montagne, A., Barnes, S. R., Sweeney, M. D., Halliday, M. R., Sagare, A. P., Zhao, Z., et al. (2015). Blood-Brain Barrier Breakdown in the Aging Human Hippocampus. Neuron 85(2), 296-302.
111. Moody, D.M. et al., (1995) Periventricular Venous Collagenosis: Association With Leukoaraiosis, Radiology. 194, 469-476.
112. Morgan, D. (2011). Immunotherapy for Alzheimer's disease. J. Intern. Med. 269(1) 54-63.
113. Muhs, A., Hickman, D. T., Pihlgren, M., Chuard, N., Giriens, V., Meerschman, C., et al. (2007). Liposomal vaccines with conformation-specific amyloid peptide antigens define immune response and efficacy in APP transgenic mice. Proc. Nat.l Acad. Sci. USA, 104(23), 9810-9815.
114. Nagele,R. G., D'Andrea, M.R., Lee, H., Venkataraman, V., and Wang, H. Y. (2003). Astrocytes accumulate Abeta 42 and give rise to astrocytic amyloid plaques in Alzheimer's disease brains. Brain Res. 971, 197-209.
115. Nascimento, C. M. C., Teixeira, C. V. L., Gobbi, L. T. B., Gobbi, S., and Stella, F. (2012). A controlled clinical trial on the effects of exercise on neuropsychiatric disorders and instrumental activities in women with Alzheimer's disease. Brazil. J. Physic. Ther. 16(3), 197-204. doi:10.1590/S1413-35552012005000017
116. National Heart, Lung, and Blood Institute. What is Sleep Apnea? US Department of Health and Human Services, 2012. Available from URL: http://www.nhlbi.nih.gov/health/health-topics/topics/sleepapnea
117. Nichol, K. E., Poon, W. W., Parachikova, A. I., Cribbs, D. H., Glabe, C. G., and Cotman, C. W. (2008). Exercise alters the immune profile in Tg2576 Alzheimer mice toward a response coincident with improved cognitive performance and decreased amyloid. J. Neuroinflam. 5(1), 13. doi:10.1186/1742-2094-5-13
118. Nicolau, C., Greferath, R., Balaban, T. S., Lazarte, J. E., and Hopkins, R. J. (2002). A liposome-based therapeutic vaccine against β-amyloid plaques on the pancreas of transgenic NORBA mice. Proc. Nat.l Acad. Sci. USA, 99(4), 2332-2337.
119. Nimmrich, V., and Eckert, A. (2013). Calcium channel blockers and dementia. Brit. J. Pharmacol. 169(6), 1203-10. doi:10.1111/bph.12240
120. Okonkwo, O. C., Schultz, S. A., Oh, J. M., Larson, J., Edwards, D., Cook, D., et al. (2014). Physical activity attenuates age-related biomarker alterations in preclinical AD. Neurol. 83(19), 1753-60. doi:10.1212/WNL.0000000000000964.
121. Olsson, E., Karlström, B., Kilander, L., Byberg, L., Cederholm, T., and Sjögren, P. (2015). Dietary patterns and cognitive dysfunction in a 12-year follow-up study of 70 year old men. J. Alzheimer's Disease 43(1), 109-19. doi:10.3233/JAD-140867
122. Ooms, S., Overeem, S., Besse, K., Rikkert, M. O., Verbeek, M., and Claassen, J. A. H. R. (2014). Effect of 1 night of total sleep deprivation on cerebrospinal fluid β-amyloid 42 in healthy middle-aged men: a randomized clinical trial. JAMA Neurol. 71(8), 971-7. doi:10.1001/jamaneurol.2014.1173
123. Origlia, N., Righi, M., Capsoni, S., Cattaneo, A., Fang, F., Stern, D. M., et al. (2008). Receptor for advanced glycation end product-dependent activation of p38 mitogen-activated protein kinase contributes to amyloid-β-mediated cortical synaptic dysfunction. J. Neurosci. 28(13), 3521-3530.
124. Origlia, N., Bonadonna, C., Rosellini, A., Leznik, E., Arancio, O., Yan, S. S. and Domenici, L. (2010). Microglial receptor for advanced glycation end product-dependent signal pathway drives β-amyloid-induced synaptic depression and long-term depression impairment in entorhinal cortex. J. Neurosci. 30(34), 11414-11425.
125. Pan, W., and Kastin, A. J. (2014). Can sleep apnea cause Alzheimer's disease? Neurosci. Biobehav. Rev. 47, 656-669. doi:10.1016/j.neubiorev.2014.10.019
126. Paoli, A., Bianco, A., Damiani, E., & Bosco, G. (2014). Ketogenic diet in neuromuscular and neurodegenerative diseases. BioMed Res. Internat. 2014. doi:10.1155/2014/474296
127. Pardridge, W. M. (2007). Blood-brain barrier delivery. Drug discovery today 12(1), 54-61.
128. Pettersen, J.A. et al., (2008) Microbleed Topography, Leukoaraiosis, and Cognition in Probable Alzheimer Disease From the Sunnybrook Dementia Study. Archives of Neurology 65, 790-795.
129. Qiu, W. Q. and Folstein, M. F. (2006). Insulin, insulin degrading enzyme and amyloid-beta peptide in Alzheimer's disease; review and hypothesis. Neurobiol, Aging 27, 190-198.
130. Querfurth, H. W., and LaFerla, F. M. (2010). Alzheimer's disease. N. Engl. J. Med. 362(4), 329-344. doi:10.1056/NEJMra0909142
131. Racke, M. M., Boone, L. I., Hepburn, D. L., Parsadainian, M., Bryan, M. T., Ness, D. K., et al. (2005). Exacerbation of cerebral amyloid angiopathy-associated microhemorrhage in amyloid precursor protein transgenic mice by immunotherapy is dependent on antibody recognition of deposited forms of amyloid β. J. Neurosci., 25(3), 629-636.
132. Rajapaksha, T. W., Eimer, W. A., Bozza, T. C., and Vassar, R. (2011). The Alzheimer β-secretase enzyme BACE1 is required for accurate axon guidance of olfactory sensory neurons and normal glomerulus formation in the olfactory bulb. Mol. Neurodegener. 6, 88.
133. Reppert, S. M., and Weaver, D. R. (2001). Molecular Analysis of Mammalian Circadian Rhythms. Annu. Rev. Physiol. 63, 647-76.
134. Revesz, T., Holton, J. L., Lashley, T., Plant, G., Rostagno, A., Ghiso, J., and Frangione, B. (2002). Sporadic and familial cerebral amyloid angiopathies. Brain pathology 12(3), 343-357
135. Revesz, T., Ghiso, J., Lashley, T., Plant, G., Rostagno, A., Frangione, B., and Holton, J. L. (2003). Cerebral Amyloid Angiopathies: A Pathologic, Biochemical, and Genetic View. J. Neuropathol. Exp. Neurol. 62(9), 885-98.
136. Reynolds, C. A., Gatz, M., Prince, J. A., Berg, S., and Pedersen, N. L. (2010). Serum lipid levels and cognitive change in late life. J. Am. Geriatrics Soiety. 58(3), 501- doi:10.1111/j.1532-5415.2010.02739.x
137. Roher, A. E., Esh, C., Kokjohn, T. A., Kalback, W., Luehrs, D. C., Seward, J. D., et al. (2003). Circle of willis atherosclerosis is a risk factor for sporadic Alzheimer's disease. Arteriosclerosis, Thromb. Vasc. Biol. 23(11), 2055-62. doi:10.1161/01.ATV.0000095973.42032.44
138. Ross, R. (1993). The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 362, 801-809.
139. Rothman, S. M., Herdener, N., Frankola, K. A., Mughal, M. R., and Mattson, M. P. (2013). Chronic mild sleep restriction accentuates contextual memory impairments, and accumulations of cortical Aβ and pTau in a mouse model of Alzheimer's disease. Brain Res. 1529, 200-8. doi:10.1016/j.brainres.2013.07.010
140. Sabbagh, M. N., Agro, A., Bell, J., Aisen, P. S., Schweizer, E., and Galasko, D. (2011). PF-04494700, an Oral Inhibitor of Receptor For Advanced Glycation End Products (RAGE), in Alzheimer's disease. Alzheimer disease and associated disorders 25(3), 206.
141. Sagare, A. P., Bell, R. D., and Zlokovic, B. V. (2013). Neurovascular defects and faulty amyloid-b vascular clearance in Alzheimer's disease. J. Alzheimer's Disease 33, S87-S100.
142. Saito, S., and Ihara, M. (2014). New therapeutic approaches for Alzheimer's disease and cerebral amyloid angiopathy. Frontiers in Aging Neuroscience 6(October), 290 doi:10.3389/fnagi.2014.00290
143. Sakurai, H., Hanyu, H., Sato, T., Kume, K., Hirao, K., Kanetaka, H., and Iwamoto, T. (2013). Effects of cilostazol on cognition and regional cerebral blood flow in patients with Alzheimer's disease and cerebrovascular disease: a pilot study. Geriatrics Gerontology Internat. 13(1), 90-7. doi:10.1111/j.1447-0594.2012.00866.x
144. Samadi, H., and Sultzer, D. (2011). Solanezumab for Alzheimer's disease. Expert Opinion on Biological Therapy, 11(6), 787-798.
145. Schley, D., Carare-Nnadi, R., Please, C. P., Perry, V. H., and Weller, R. O. (2006). Mechanisms to explain the reverse perivascular transport of solutes out of the brain. J. Theor. Biol. 238(4), 962-74. doi:10.1016/j.jtbi.2005.07.005
146. Selkoe, D. J. (2001). Alzheimer's Disease: Genes, Proteins, and Therapy. Physiol. Rev. 81(2), 741-766.
147. Sengillo, J. D., Winkler, E. A., Walker, C. T., Sullivan, J. S., Johnson, M., Zlokovic, B. V. (2013). Deficiency in mural vascular cells coincides with blood-brain barrier disruption in Alzheimer's disease. Brain Pathol, 23, 303-310.
148. Shibata, M., Yamada, S., Kumar, S. R., Calero, M., Bading, J., Frangione, B., et al. (2000). Clearance of Alzheimer's amyloid-β(1-40) peptide from brain by LDL receptor-related protein-1 at the blood brain barrier. J. Clin. Invest. 106, 1489-1499.
149. Sigurdsson, E. M., Knudsen, E., Asuni, A., Fitzer-Attas, C., Sage, D., Quartermain, D., et al. (2004). An attenuated immune response is sufficient to enhance cognition in an Alzheimer's disease mouse model immunized with amyloid-β derivatives. J. Neurosci., 24(28), 6277-6282.
150. Sperling, R. A., Aisen P. S., Beckett, L. A., Bennett, D. A., Craft, S., Fagan, A. M., Iwatsubo, T., et al. (2011). 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. 7, 280-292.
151. Spira, A. P., Gamaldo, A. a, An, Y., Wu, M. N., Simonsick, E. M., Bilgel, M., et al. (2013). Self-reported sleep and β-amyloid deposition in community-dwelling older adults. JAMA Neurol. 70(12), 1537-43. doi:10.1001/jamaneurol.2013.4258
152. Srikanth, V., Maczurek, A., Phan, T., Steele, M., Westcott, B., Juskiw, D., and Münch, G. (2011). Advanced glycation endproducts and their receptor RAGE in Alzheimer's disease. Neurobiol. Aging 32(5), 763-77. doi:10.1016/j.neurobiolaging.2009.04.016
153. Sterniczuk, R., Dyck, R. H., Laferla, F. M., and Antle, M. C. (2010). Characterization of the 3xTg-AD mouse model of Alzheimer's disease: part 1. Circadian changes. Brain Res. 1348, 139-48. doi:10.1016/j.brainres.2010.05.013
154. Stone, J., Kleijn, H. J., Dockendorf, M., Ma, L., Palcza, J., Tseng, J., et al. (2013). Consistency of Bace inhibitor-mediated brain amyloid production inhibition by MK-8931 in Alzheimer's disease patients and healthy young adults. Alzheimer's & Dementia: The Journal of the Alzheimer's Association, 9(4), P690-P691.
155. Stranahan, A. M., Martin, B., & Maudsley, S. (2012). Anti-Inflammatory Effects of Physical Activity in Relationship to Improved Cognitive Status in Humans and Mouse Models of Alzheimers Disease. Current Alzheimer Research 9(1), 86-92. doi:10.2174/156720512799015019
156. Suttanon, P., Hill, K. D., Said, C. M., Williams, S. B., Byrne, K. N., LoGiudice, D., et al. (2012). Feasibility, safety and preliminary evidence of the effectiveness of a home-based exercise programme for older people with Alzheimer's disease: a pilot randomized controlled trial. Clin. Rehab. 27(5), 427-38. doi:10.1177/0269215512460877
157. Szentistvanyi, I., Patlak, C. S., Elliss, R. A., and Cserr, H. F (1984). Drainage of interstitial fluid from different regions of rat brain. Am. J. Physiol. 246, F835-F844.
158. Takakura, S., Sogabe, K., Satoh, H., Mori, J., Fujiwara, T., Totsuka, Z., et al. (1992). Nilvadipine as a neuroprotective calcium entry blocker in a rat model of global cerebral ischemia. A comparative study with nicardipine hydrochloride. Neurosci. Lett. 141(2), 199-202.
159. Tang, B. L., and Chua, C. E. L. (2008). SIRT1 and neuronal diseases. Mol. Aspects of Med. 29(3), 187-200. doi:10.1016/j.mam.2007.02.001
160. Tanzi, R. E., Moir, R. D., and Wagner, S. L. (2004). Clearance of Alzheimer's Abeta peptide: the many roads to perdition. Neuron 43(5), 605-608.
161. Thal, D. R. Sassing, I., Schultz, C., Haas, C., Braak, E., and Braak, H. (1999). Fleecy amyloid deposits in the internal layers of the human entorhinal cortex are comprised of N-terminal truncated fragments of Ab. J. Neuropathol Exp. Neurol. 58, 210-216.
162. Thal, D. R., Griffin, W. S. T., de Vos, R. A., and Ghebremedhin, E. (2008). Cerebral amyloid angiopathy and its relationship to Alzheimer's disease. Acta neuropathologica 115(6), 599-609.
163. Tolppanen, A.-M., Solomon, A., Soininen, H., and Kivipelto, M. (2012). Midlife vascular risk factors and Alzheimer's disease: evidence from epidemiological studies. J. Alzheimer's Disease 32(3), 531-40. doi:10.3233/JAD-2012-120802
164. Vassar, R., Bennett, B. D., Babu-Khan, S., Kahn, S., Mendiaz, E. A., Denis, P., et al (1999). β-Secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE. Science 286(5440), 735-741.
165. Venturelli, M., Scarsini, R., and Schena, F. (2011). Six-month walking program changes cognitive and ADL performance in patients with Alzheimer. Am. J. Alzheimer's Disease and Other Dementias 26(5), 381-8. doi:10.1177/1533317511418956
166. Verbeek, M. M., Van Nostrand, W. E., Otte-Höller, I., Wesseling, P., and De Waal, R. M. (2000). Amyloid-beta-induced degeneration of human brain pericytes is dependent on the apolipoprotein E genotype. Ann. N. Y. Acad. Sci. 903, 187-99.
167. Videnovic, A., Lazar, A. S., Barker, R. a, and Overeem, S. (2014). "The clocks that time us"-circadian rhythms in neurodegenerative disorders. Nat. Rev. Neurol. 10(12), 683-693. doi:10.1038/nrneurol.2014.206
168. Vidoni, E. D., Van Sciver, A., Johnson, D. K., He, J., Honea, R., Haines, B., et al. (2012). A community-based approach to trials of aerobic exercise in aging and Alzheimer's disease. Contemp. Clin. Trials, 33(6), 1105-16. doi:10.1016/j.cct.2012.08.002
169. Viswanathan, A., Rocca, W. A., and Tzourio, C. (2009). Vascular risk factors and dementia. Neurol. Views & Rev. 72, 368-74.
170. Voss, M. W., Vivar, C., Kramer, A. F., and van Praag, H. (2013). Bridging animal and human models of exercise-induced brain plasticity. Trends in Cog. Sci. 17(10), 525- doi:10.1016/j.tics.2013.08.001
171. Wan, R., Weigand, L. a, Bateman, R., Griffioen, K., Mendelowitz, D., and Mattson, M. P. (2014). Evidence that BDNF regulates heart rate by a mechanism involving increased brainstem parasympathetic neuron excitability. J. Neurochem. 129(4), 573-80. doi:10.1111/jnc.12656
172. Wang, J., Ho, L., Qin, W., Rocher, A. B., Seror, I., Humala, N., et al. (2005). Caloric restriction attenuates beta-amyloid neuropathology in a mouse model of Alzheimer's disease. FASEB J. 19(6), 659-661. doi:10.1096/fj.04-3182fje
173. Wang, P., and Olbricht, W. L. (2011). Fluid mechanics in the perivascular space. J. Theor. Biol. 274(1),52-7. doi:10.1016/j.jtbi.2011.01.014.
174. Weksler, M. E., Relkin, N., Turkenich, R., LaRusse, S., Zhou, L., and Szabo, P. (2002). Patients with Alzheimer disease have lower levels of serum anti-amyloid peptide antibodies than healthy elderly individuals. Exp. Gerontology 37(7), 943-948.
175. Weller, R. O. (2005). Microscopic morphology and histology of the human meninges. Morphologie. 89(284), 22-34.
176. Weller, R. O., Subash, M., Preston, S. D., Mazanti, I., and Carare, R. O. (2008). Perivascular drainage of amyloid-beta peptides from the brain and its failure in cerebral amyloid angiopathy and Alzheimer's disease. Brain Pathol. 18(2), 253-66. doi:10.1111/j.1750-3639.2008.00133.x
177. Weller, R. O., Boche, D., and Nicoll, J. a R. (2009). Microvasculature changes and cerebral amyloid angiopathy in Alzheimer's disease and their potential impact on therapy. Acta Neuropathol. 118(1), 87-102. doi:10.1007/s00401-009-0498-z
178. Weller, R. O., Galea, I., Carare, R. O., and Minagar, A. (2010). Pathophysiology of the lymphatic drainage of the central nervous system: Implications for pathogenesis and therapy of multiple sclerosis. Pathophysiol. Off. J.Internat. Soc. Pathophysiol. 17(4), 295-306. doi:10.1016/j.pathophys.2009.10.007
179. Wiessner, C., Wiederhold, K. H., Tissot, A. C., Frey, P., Danner, S., Jacobson, L. H., et al. (2011). The second-generation active Aβ immunotherapy CAD106 reduces amyloid accumulation in APP transgenic mice while minimizing potential side effects. J. Neurosci. 31(25), 9323-9331.
180. Wilcock, D. M., Rojiani, A., Rosenthal, A., Levkowitz, G., Subbarao, S., Alamed, J., Wilson, D., et al. (2004). Passive amyloid immunotherapy clears amyloid and transiently activated microglia in a transgenic mouse model of amyloid deposition. J. Neurosci. 24(27), 6144-6151.
181. Winblad, B., Andreasen, N., Minthon, L., Floesser, A., Imbert, G., Dumortier, T., et al. (2012). Safety, tolerability, and antibody response of active Aβ immunotherapy with CAD106 in patients with Alzheimer's disease: randomised, double-blind, placebocontrolled, first-in-human study. The Lancet. Neurology 11(7), 597-604. doi.org/10.1016/S1474-4422(12)70140-0
182. Winchester, J., Dick, M. B., Gillen, D., Reed, B., Miller, B., Tinklenberg, J., et al.(2013). Walking stabilizes cognitive functioning in Alzheimer's disease (AD) across one year. Arch. Gerontology Geriatrics 56(1), 96-103. doi:10.1016/j.archger.2012.06.016
183. Witte, A. V., Fobker, M., Gellner, R., Knecht, S., and Floel, A. (2009). Caloric restriction improves memory in elderly humans. Proc. Nat.l Acad. Sci. USA 106(4), 1255-60. doi:10.1073/pnas.0808587106
184. Wu, P., Shen, Q., Dong, S., Xu, Z., Tsien, J. Z., and Hu, Y. (2008). Calorie restriction ameliorates neurodegenerative phenotypes in forebrain-specific presenilin-1 and presenilin-2 double knockout mice. Neurobiol. Aging 29(10), 1502-1511. doi:10.1016/j.neurobiolaging.2007.03.028
185. Wyatt, A. R., Yerbury, J. J., Dabbs, R. A., and Wilson, M. R. (2012). Roles of extracellular chaperones in amyloidosis. J. Mol. Biol. 421, 499-516.
186. Wyss-Coray, T., Loike, J. D., Brionne, T. C., Lu, E., Anakov, R., Yan, F., et al. (2003). Adult mouse astrocytes degrade amyloid-b in vitro and in vivo. Nat. Med. 9, 453-457.
187. Xie, L., Kang, H., Xu, Q., Chen, M. J., Liao, Y., Thiyagarajan, M., et al. (2013). Sleep drives metabolite clearance from the adult brain. Science 342(6156), 373-7. doi:10.1126/science.1241224.
188. Yan, S. S., Chen, D., Yan, S., Guo, L., and Chen, J. X. (2012). RAGE is a key cellular target for Aβ-induced perturbation in Alzheimer's disease. Frontiers in Bioscience 4, 240.
189. Yanagisawa, D. Shirai, N., Amatsubo, T., Taguchi, H., Hirao, K., Urushitani, M., Morikawa, S. et al. (2010). Relationship between tautomeric stuctures of curcumin derivatives and their Abeta-binding activities in the context of therapies for Alzheimer's disease. Biomaterials 31(14), 4179-4185.
190. Yang, L., Kress, B. T., Weber, H. J., Thiyagarajan, M., Wang, B., Deane, R., et al. (2013). Evaluating glymphatic pathway function utilizing clinically relevant intrathecal infusion of CSF tracer. J. Transl. Med. 11(1), 107. doi:10.1186/1479-5876-11-107
191. Yannakoulia, M., Kontogianni, M., and Scarmeas, N. (2014). Cognitive health and Mediterranean: Just diet or lifestyle pattern? Ageing Res. Rev. [in press 2014]. doi:10.1016/j.arr.2014.10.003
192. Yasojima, K., Akiyama, H., McGeer, E. G., and McGeer, P.L. (2001). Reduced neprilysin in high plaque areas of Alzheimer's disease brain: A possible relationship to deficient degradation of beta-amyloid peptide. Neurosci. Lett. 297, 97-100.
193. Zelinski, E. L., Deibel, S. H., and McDonald, R. J. (2014). The trouble with circadian clock dysfunction: multiple deleterious effects on the brain and body. Neurosci. Biobehav. Rev. 40, 80-101. doi:10.1016/j.neubiorev.2014.01.007
194. Zhou, L., Barão, S., Laga, M., Bockstael, K., Borgers, M., Gijsen, H., et al. (2012). The neural cell adhesion molecules L1 and CHL1 are cleaved by BACE1 protease in vivo. J. Biol. Chem. 287(31), 25927-25940.