Impaired Aß clearance: A potential link between atherosclerosis and Alzheimer's disease

Frontiers in Aging Neuroscience

Volumn 7, Issue MAY, 2015, Pages

  Gupta, Ajay ^a,b   Iadecola, Costantino ^a  

^a FEIL FAMILY BRAIN AND MIND RESEARCH INSTITUTE   (United States)

^b WEILL CORNELL MEDICAL COLLEGE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMYLOID BETA PROTEIN; AMYLOID PRECURSOR PROTEIN; PITTSBURGH COMPOUND B;

ALZHEIMER DISEASE; ARTERIAL STIFFNESS; ARTERY OCCLUSION; ARTICLE; ATHEROGENESIS; BRAIN ATHEROSCLEROSIS; BRAIN CIRCULUS ARTERIOSUS; BRAIN LEVEL; CLEARANCE; DISEASE ASSOCIATION; HISTOPATHOLOGY; HUMAN; MICROANGIOPATHY; NONHUMAN; PATHOPHYSIOLOGY; POSITRON EMISSION TOMOGRAPHY; PROTEIN METABOLISM; PROTEIN PROCESSING; RISK FACTOR;

EID: 84931263025     PISSN: None     EISSN: 16634365     Source Type: Journal    
DOI: 10.3389/fnagi.2015.00115     Document Type: Article

References (78)

1. Alsop, D.C., Detre, J.A., and Grossman, M. (2000). Assessment of cerebral blood flow in Alzheimer's disease by spin-labeled magnetic resonance imaging. Ann Neurol 47, 93-100.
2. Barnes, D.E., and Yaffe, K. (2011). The projected effect of risk factor reduction on Alzheimer's disease prevalence. Lancet Neurol 10, 819-828. doi: 10.1016/s1474-4422(11)70072-2.
3. Beach, T.G., Wilson, J.R., Sue, L.I., Newell, A., Poston, M., Cisneros, R., Pandya, Y., Esh, C., Connor, D.J., Sabbagh, M., Walker, D.G., and Roher, A.E. (2007). Circle of Willis atherosclerosis: association with Alzheimer's disease, neuritic plaques and neurofibrillary tangles. Acta Neuropathol 113, 13-21. doi: 10.1007/s00401-006-0136-y.
4. Bell, R.D., and Zlokovic, B.V. (2009). Neurovascular mechanisms and blood-brain barrier disorder in Alzheimer's disease. Acta Neuropathol 118, 103-113. doi: 10.1007/s00401- 009-0522-3.
5. Bhatt, D.L., Steg, P.G., Ohman, E.M., Hirsch, A.T., Ikeda, Y., Mas, J.L., Goto, S., Liau, C.S., Richard, A.J., Rother, J., and Wilson, P.W. (2006). International prevalence, recognition, and treatment of cardiovascular risk factors in outpatients with atherothrombosis. Jama 295, 180-189. doi: 10.1001/jama.295.2.180.
6. Bowler, J.V. (2007). Modern concept of vascular cognitive impairment. Br Med Bull 83, 291- 305. doi: 10.1093/bmb/ldm021.
7. Breteler, M.M. (2000). Vascular risk factors for Alzheimer's disease: an epidemiologic perspective. Neurobiol Aging 21, 153-160.
8. Brookmeyer, R., Johnson, E., Ziegler-Graham, K., and Arrighi, H.M. (2007). Forecasting the global burden of Alzheimer's disease. Alzheimers Dement 3, 186-191. doi: 10.1016/j.jalz.2007.04.381.
9. Carare, R.O., Hawkes, C.A., Jeffrey, M., Kalaria, R.N., and Weller, R.O. (2013). Review: cerebral amyloid angiopathy, prion angiopathy, CADASIL and the spectrum of protein elimination failure angiopathies (PEFA) in neurodegenerative disease with a focus on therapy. Neuropathol Appl Neurobiol 39, 593-611. doi: 10.1111/nan.12042.
10. Caravaggio, J.W., Hasu, M., Maclaren, R., Thabet, M., Raizman, J.E., Veinot, J.P., Marcel, Y.L., Milne, R.W., and Whitman, S.C. (2013). Insulin-degrading enzyme deficiency in bone marrow cells increases atherosclerosis in LDL receptor-deficient mice. Cardiovasc Pathol 22, 458-464. doi: 10.1016/j.carpath.2013.03.006.
11. Chi, N.F., Chien, L.N., Ku, H.L., Hu, C.J., and Chiou, H.Y. (2013). Alzheimer disease and risk of stroke: a population-based cohort study. Neurology 80, 705-711. doi: 10.1212/WNL.0b013e31828250af.
12. Chui, H.C., Zheng, L., Reed, B.R., Vinters, H.V., and Mack, W.J. (2012). Vascular risk factors and Alzheimer's disease: are these risk factors for plaques and tangles or for concomitant vascular pathology that increases the likelihood of dementia? An evidence-based review. Alzheimers Res Ther 4, 1. doi: 10.1186/alzrt98.
13. Dai, W., Lopez, O.L., Carmichael, O.T., Becker, J.T., Kuller, L.H., and Gach, H.M. (2009). Mild cognitive impairment and alzheimer disease: patterns of altered cerebral blood flow at MR imaging. Radiology 250, 856-866. doi: 10.1148/radiol.2503080751.
14. De Meyer, G.R., De Cleen, D.M., Cooper, S., Knaapen, M.W., Jans, D.M., Martinet, W., Herman, A.G., Bult, H., and Kockx, M.M. (2002). Platelet phagocytosis and processing of beta-amyloid precursor protein as a mechanism of macrophage activation in atherosclerosis. Circ Res 90, 1197-1204.
15. Deschaintre, Y., Richard, F., Leys, D., and Pasquier, F. (2009). Treatment of vascular risk factors is associated with slower decline in Alzheimer disease. Neurology 73, 674-680. doi: 10.1212/WNL.0b013e3181b59bf3.
16. Dolan, H., Crain, B., Troncoso, J., Resnick, S.M., Zonderman, A.B., and Obrien, R.J. (2010). Atherosclerosis, dementia, and Alzheimer disease in the Baltimore Longitudinal Study of Aging cohort. Ann Neurol 68, 231-240. doi: 10.1002/ana.22055.
17. Faraco, G., Park, L., Zhou, P., Luo, W., Paul, S.M., Anrather, J., and Iadecola, C. (2015). Hypertension enhances Abeta-induced neurovascular dysfunction, promotes betasecretase activity, and leads to amyloidogenic processing of APP. J Cereb Blood Flow Metab. doi: 10.1038/jcbfm.2015.79.
18. Glenner, G.G., and Wong, C.W. (1984). Alzheimer's disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem Biophys Res Commun 120, 885-890.
19. Gorgone, G., Ursini, F., Altamura, C., Bressi, F., Tombini, M., Curcio, G., Chiovenda, P., Squitti, R., Silvestrini, M., Ientile, R., Pisani, F., Rossini, P.M., and Vernieri, F. (2009). Hyperhomocysteinemia, intima-media thickness and C677T MTHFR gene polymorphism: a correlation study in patients with cognitive impairment. Atherosclerosis 206, 309-313. doi: 10.1016/j.atherosclerosis.2009.02.028.
20. Gupta, A., Nair, S., Schweitzer, A.D., Kishore, S., Johnson, C.E., Comunale, J.P., Tsiouris, A.J., and Sanelli, P.C. (2012). Neuroimaging of cerebrovascular disease in the aging brain. Aging Dis 3, 414-425.
21. Hawkes, C.A., Hartig, W., Kacza, J., Schliebs, R., Weller, R.O., Nicoll, J.A., and Carare, R.O. (2011). Perivascular drainage of solutes is impaired in the ageing mouse brain and in the presence of cerebral amyloid angiopathy. Acta Neuropathol 121, 431-443. doi: 10.1007/s00401-011-0801-7.
22. Hawkes, C.A., Jayakody, N., Johnston, D.A., Bechmann, I., and Carare, R.O. (2014). Failure of perivascular drainage of beta-amyloid in cerebral amyloid angiopathy. Brain Pathol 24, 396-403. doi: 10.1111/bpa.12159.
23. Hofman, A., Ott, A., Breteler, M.M., Bots, M.L., Slooter, A.J., Van Harskamp, F., Van Duijn, C.N., Van Broeckhoven, C., and Grobbee, D.E. (1997). Atherosclerosis, apolipoprotein E, and prevalence of dementia and Alzheimer's disease in the Rotterdam Study. Lancet 349, 151-154. doi: 10.1016/s0140-6736(96)09328-2.
24. Honig, L.S., Kukull, W., and Mayeux, R. (2005). Atherosclerosis and AD: analysis of data from the US National Alzheimer's Coordinating Center. Neurology 64, 494-500. doi: 10.1212/01.wnl.0000150886.50187.30.
25. Hughes, T.M., Kuller, L.H., Barinas-Mitchell, E.J., Mcdade, E.M., Klunk, W.E., Cohen, A.D., Mathis, C.A., Dekosky, S.T., Price, J.C., and Lopez, O.L. (2014). Arterial stiffness and beta-amyloid progression in nondemented elderly adults. JAMA Neurol 71, 562-568. doi: 10.1001/jamaneurol.2014.186.
26. Iadecola, C. (2003a). Atherosclerosis and neurodegeneration: unexpected conspirators in Alzheimer's dementia. Arterioscler Thromb Vasc Biol 23, 1951-1953. doi: 10.1161/01.atv.0000102660.99744.85.
27. Iadecola, C. (2003b). Cerebrovascular effects of amyloid-beta peptides: mechanisms and implications for Alzheimer's dementia. Cell Mol Neurobiol 23, 681-689.
28. Iadecola, C. (2004). Neurovascular regulation in the normal brain and in Alzheimer's disease. Nat Rev Neurosci 5, 347-360. doi: 10.1038/nrn1387.
29. Iadecola, C. (2010). The overlap between neurodegenerative and vascular factors in the pathogenesis of dementia. Acta Neuropathol 120, 287-296. doi: 10.1007/s00401-010- 0718-6.
30. Iadecola, C. (2013). The pathobiology of vascular dementia. Neuron 80, 844-866. doi: 10.1016/j.neuron.2013.10.008.
31. Iadecola, C., and Gorelick, P.B. (2003). Converging pathogenic mechanisms in vascular and neurodegenerative dementia. Stroke 34, 335-337.
32. Iadecola, C., Zhang, F., Niwa, K., Eckman, C., Turner, S.K., Fischer, E., Younkin, S., Borchelt, D.R., Hsiao, K.K., and Carlson, G.A. (1999). SOD1 rescues cerebral endothelial dysfunction in mice overexpressing amyloid precursor protein. Nat Neurosci 2, 157-161. doi: 10.1038/5715.
33. Iliff, J.J., Lee, H., Yu, M., Feng, T., Logan, J., Nedergaard, M., and Benveniste, H. (2013). Brain-wide pathway for waste clearance captured by contrast-enhanced MRI. J Clin Invest 123, 1299-1309. doi: 10.1172/jci67677.
34. Jurasic, M.J., Popovic, I.M., Morovic, S., Trkanjec, Z., Seric, V., and Demarin, V. (2009). Can beta stiffness index be proposed as risk factor for dementia. J Neurol Sci 283, 13-16. doi: 10.1016/j.jns.2009.02.339.
35. Kang, J., Lemaire, H.G., Unterbeck, A., Salbaum, J.M., Masters, C.L., Grzeschik, K.H., Multhaup, G., Beyreuther, K., and Muller-Hill, B. (1987). The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor. Nature 325, 733-736. doi: 10.1038/325733a0.
36. Koike, M.A., Green, K.N., Blurton-Jones, M., and Laferla, F.M. (2010). Oligemic hypoperfusion differentially affects tau and amyloid-{beta}. Am J Pathol 177, 300-310. doi: 10.2353/ajpath.2010.090750.
37. Kress, B.T., Iliff, J.J., Xia, M., Wang, M., Wei, H.S., Zeppenfeld, D., Xie, L., Kang, H., Xu, Q., Liew, J.A., Plog, B.A., Ding, F., Deane, R., and Nedergaard, M. (2014). Impairment of paravascular clearance pathways in the aging brain. Ann Neurol 76, 845-861. doi: 10.1002/ana.24271.
38. Larson, E.B., Yaffe, K., and Langa, K.M. (2013). New insights into the dementia epidemic. N Engl J Med 369, 2275-2277. doi: 10.1056/NEJMp1311405.
39. Li, L., Zhang, X., Yang, D., Luo, G., Chen, S., and Le, W. (2009). Hypoxia increases Abeta generation by altering beta- and gamma-cleavage of APP. Neurobiol Aging 30, 1091- 1098. doi: 10.1016/j.neurobiolaging.2007.10.011.
40. Miners, J.S., Baig, S., Palmer, J., Palmer, L.E., Kehoe, P.G., and Love, S. (2008). Abetadegrading enzymes in Alzheimer's disease. Brain Pathol 18, 240-252. doi: 10.1111/j.1750-3639.2008.00132.x.
41. Neltner, J.H., Abner, E.L., Baker, S., Schmitt, F.A., Kryscio, R.J., Jicha, G.A., Smith, C.D., Hammack, E., Kukull, W.A., Brenowitz, W.D., Van Eldik, L.J., and Nelson, P.T. (2014). Arteriolosclerosis that affects multiple brain regions is linked to hippocampal sclerosis of ageing. Brain 137, 255-267. doi: 10.1093/brain/awt318.
42. Newman, A.B., Fitzpatrick, A.L., Lopez, O., Jackson, S., Lyketsos, C., Jagust, W., Ives, D., Dekosky, S.T., and Kuller, L.H. (2005). Dementia and Alzheimer's disease incidence in relationship to cardiovascular disease in the Cardiovascular Health Study cohort. J Am Geriatr Soc 53, 1101-1107. doi: 10.1111/j.1532-5415.2005.53360.x.
43. Ngandu, T., Lehtisalo, J., Solomon, A., Levalahti, E., Ahtiluoto, S., Antikainen, R., Backman, L., Hanninen, T., Jula, A., Laatikainen, T., Lindstrom, J., Mangialasche, F., Paajanen, T., Pajala, S., Peltonen, M., Rauramaa, R., Stigsdotter-Neely, A., Strandberg, T., Tuomilehto, J., Soininen, H., and Kivipelto, M. (2015). A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial. Lancet. doi: 10.1016/s0140-6736(15)60461-5.
44. Niwa, K., Carlson, G.A., and Iadecola, C. (2000a). Exogenous A beta1-40 reproduces cerebrovascular alterations resulting from amyloid precursor protein overexpression in mice. J Cereb Blood Flow Metab 20, 1659-1668. doi: 10.1097/00004647-200012000- 00005.
45. Niwa, K., Kazama, K., Younkin, L., Younkin, S.G., Carlson, G.A., and Iadecola, C. (2002a). Cerebrovascular autoregulation is profoundly impaired in mice overexpressing amyloid precursor protein. Am J Physiol Heart Circ Physiol 283, H315-323. doi: 10.1152/ajpheart.00022.2002.
46. Niwa, K., Kazama, K., Younkin, S.G., Carlson, G.A., and Iadecola, C. (2002b). Alterations in cerebral blood flow and glucose utilization in mice overexpressing the amyloid precursor protein. Neurobiol Dis 9, 61-68. doi: 10.1006/nbdi.2001.0460.
47. Niwa, K., Porter, V.A., Kazama, K., Cornfield, D., Carlson, G.A., and Iadecola, C. (2001). A beta-peptides enhance vasoconstriction in cerebral circulation. Am J Physiol Heart Circ Physiol 281, H2417-2424.
48. Niwa, K., Younkin, L., Ebeling, C., Turner, S.K., Westaway, D., Younkin, S., Ashe, K.H., Carlson, G.A., and Iadecola, C. (2000b). Abeta 1-40-related reduction in functional hyperemia in mouse neocortex during somatosensory activation. Proc Natl Acad Sci U S A 97, 9735-9740.
49. Norton, S., Matthews, F.E., Barnes, D.E., Yaffe, K., and Brayne, C. (2014). Potential for primary prevention of Alzheimer's disease: an analysis of population-based data. Lancet Neurol 13, 788-794. doi: 10.1016/s1474-4422(14)70136-x.
50. Okamoto, Y., Yamamoto, T., Kalaria, R.N., Senzaki, H., Maki, T., Hase, Y., Kitamura, A., Washida, K., Yamada, M., Ito, H., Tomimoto, H., Takahashi, R., and Ihara, M. (2012). Cerebral hypoperfusion accelerates cerebral amyloid angiopathy and promotes cortical microinfarcts. Acta Neuropathol 123, 381-394. doi: 10.1007/s00401-011-0925-9.
51. Reed, B., Villeneuve, S., Mack, W., Decarli, C., Chui, H.C., and Jagust, W. (2014). Associations between serum cholesterol levels and cerebral amyloidosis. JAMA Neurol 71, 195-200. doi: 10.1001/jamaneurol.2013.5390.
52. Reed, B.R., Marchant, N.L., Jagust, W.J., Decarli, C.C., Mack, W., and Chui, H.C. (2012). Coronary risk correlates with cerebral amyloid deposition. Neurobiol Aging 33, 1979- 1987. doi: 10.1016/j.neurobiolaging.2011.10.002.
53. Richard, E., Gouw, A.A., Scheltens, P., and Van Gool, W.A. (2010). Vascular care in patients with Alzheimer disease with cerebrovascular lesions slows progression of white matter lesions on MRI: the evaluation of vascular care in Alzheimer's disease (EVA) study. Stroke 41, 554-556. doi: 10.1161/strokeaha.109.571281.
54. Rodrigue, K.M., Rieck, J.R., Kennedy, K.M., Devous, M.D., Sr., Diaz-Arrastia, R., and Park, D.C. (2013). Risk factors for beta-amyloid deposition in healthy aging: vascular and genetic effects. JAMA Neurol 70, 600-606. doi: 10.1001/jamaneurol.2013.1342.
55. Roher, A.E., Esh, C., Kokjohn, T.A., Kalback, W., Luehrs, D.C., Seward, J.D., Sue, L.I., and Beach, T.G. (2003). Circle of willis atherosclerosis is a risk factor for sporadic Alzheimer's disease. Arterioscler Thromb Vasc Biol 23, 2055-2062. doi: 10.1161/01.atv.0000095973.42032.44.
56. Roher, A.E., Garami, Z., Tyas, S.L., Maarouf, C.L., Kokjohn, T.A., Belohlavek, M., Vedders, L.J., Connor, D., Sabbagh, M.N., Beach, T.G., and Emmerling, M.R. (2011). Transcranial doppler ultrasound blood flow velocity and pulsatility index as systemic indicators for Alzheimer's disease. Alzheimers Dement 7, 445-455. doi: 10.1016/j.jalz.2010.09.002.
57. Rosenberg, P.B., Mielke, M.M., Tschanz, J., Cook, L., Corcoran, C., Hayden, K.M., Norton, M., Rabins, P.V., Green, R.C., Welsh-Bohmer, K.A., Breitner, J.C., Munger, R., and Lyketsos, C.G. (2008). Effects of cardiovascular medications on rate of functional decline in Alzheimer disease. Am J Geriatr Psychiatry 16, 883-892. doi: 10.1097/JGP.0b013e318181276a.
58. Ruitenberg, A., Den Heijer, T., Bakker, S.L., Van Swieten, J.C., Koudstaal, P.J., Hofman, A., and Breteler, M.M. (2005). Cerebral hypoperfusion and clinical onset of dementia: the Rotterdam Study. Ann Neurol 57, 789-794. doi: 10.1002/ana.20493.
59. Sadleir, K.R., Bennett, D.A., Schneider, J.A., and Vassar, R. (2013). Elevated Abeta42 in aged, non-demented individuals with cerebral atherosclerosis. Curr Alzheimer Res 10, 785-789.
60. 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, 962-974. doi: 10.1016/j.jtbi.2005.07.005.
61. Silvestrini, M., Gobbi, B., Pasqualetti, P., Bartolini, M., Baruffaldi, R., Lanciotti, C., Cerqua, R., Altamura, C., Provinciali, L., and Vernieri, F. (2009). Carotid atherosclerosis and cognitive decline in patients with Alzheimer's disease. Neurobiol Aging 30, 1177-1183. doi: 10.1016/j.neurobiolaging.2007.11.008.
62. Snowdon, D.A., Greiner, L.H., Mortimer, J.A., Riley, K.P., Greiner, P.A., and Markesbery, W.R. (1997). Brain infarction and the clinical expression of Alzheimer disease. The Nun Study. Jama 277, 813-817.
63. Sun, X., He, G., Qing, H., Zhou, W., Dobie, F., Cai, F., Staufenbiel, M., Huang, L.E., and Song, W. (2006). Hypoxia facilitates Alzheimer's disease pathogenesis by up-regulating BACE1 gene expression. Proc Natl Acad Sci U S A 103, 18727-18732. doi: 10.1073/pnas.0606298103.
64. Tesco, G., Koh, Y.H., Kang, E.L., Cameron, A.N., Das, S., Sena-Esteves, M., Hiltunen, M., Yang, S.H., Zhong, Z., Shen, Y., Simpkins, J.W., and Tanzi, R.E. (2007). Depletion of GGA3 stabilizes BACE and enhances beta-secretase activity. Neuron 54, 721-737. doi: 10.1016/j.neuron.2007.05.012.
65. Thomas, T., Miners, S., and Love, S. (2015). Post-mortem assessment of hypoperfusion of cerebral cortex in Alzheimer's disease and vascular dementia. Brain 138, 1059-1069. doi: 10.1093/brain/awv025.
66. Thomas, T., Thomas, G., Mclendon, C., Sutton, T., and Mullan, M. (1996). beta-Amyloidmediated vasoactivity and vascular endothelial damage. Nature 380, 168-171. doi: 10.1038/380168a0.
67. Tibolla, G., Norata, G.D., Meda, C., Arnaboldi, L., Uboldi, P., Piazza, F., Ferrarese, C., Corsini, A., Maggi, A., Vegeto, E., and Catapano, A.L. (2010). Increased atherosclerosis and vascular inflammation in APP transgenic mice with apolipoprotein E deficiency. Atherosclerosis 210, 78-87. doi: 10.1016/j.atherosclerosis.2009.10.040.
68. Toledo, J.B., Arnold, S.E., Raible, K., Brettschneider, J., Xie, S.X., Grossman, M., Monsell, S.E., Kukull, W.A., and Trojanowski, J.Q. (2013). Contribution of cerebrovascular disease in autopsy confirmed neurodegenerative disease cases in the National Alzheimer's Coordinating Centre. Brain 136, 2697-2706. doi: 10.1093/brain/awt188.
69. Tolppanen, A.M., Lavikainen, P., Solomon, A., Kivipelto, M., Soininen, H., and Hartikainen, S. (2013). Incidence of stroke in people with Alzheimer disease: a national register-based approach. Neurology 80, 353-358. doi: 10.1212/WNL.0b013e31827f08c5.
70. Valenti, R., Pantoni, L., and Markus, H.S. (2014). Treatment of vascular risk factors in patients with a diagnosis of Alzheimer's disease: a systematic review. BMC Med 12, 160. doi: 10.1186/s12916-014-0160-z.
71. Van Oijen, M., De Jong, F.J., Witteman, J.C., Hofman, A., Koudstaal, P.J., and Breteler, M.M. (2007). Atherosclerosis and risk for dementia. Ann Neurol 61, 403-410. doi: 10.1002/ana.21073.
72. Vermeer, S.E., Prins, N.D., Den Heijer, T., Hofman, A., Koudstaal, P.J., and Breteler, M.M. (2003). Silent brain infarcts and the risk of dementia and cognitive decline. N Engl J Med 348, 1215-1222. doi: 10.1056/NEJMoa022066.
73. Wang, P., and Olbricht, W.L. (2011). Fluid mechanics in the perivascular space. J Theor Biol 274, 52-57. doi: 10.1016/j.jtbi.2011.01.014.
74. Yarchoan, M., Xie, S.X., Kling, M.A., Toledo, J.B., Wolk, D.A., Lee, E.B., Van Deerlin, V., Lee, V.M., Trojanowski, J.Q., and Arnold, S.E. (2012). Cerebrovascular atherosclerosis correlates with Alzheimer pathology in neurodegenerative dementias. Brain 135, 3749- 3756. doi: 10.1093/brain/aws271.
75. Zetterberg, H., Mortberg, E., Song, L., Chang, L., Provuncher, G.K., Patel, P.P., Ferrell, E., Fournier, D.R., Kan, C.W., Campbell, T.G., Meyer, R., Rivnak, A.J., Pink, B.A., Minnehan, K.A., Piech, T., Rissin, D.M., Duffy, D.C., Rubertsson, S., Wilson, D.H., and Blennow, K. (2011). Hypoxia due to cardiac arrest induces a time-dependent increase in serum amyloid beta levels in humans. PLoS One 6, e28263. doi: 10.1371/journal.pone.0028263.
76. Zhang, F., Eckman, C., Younkin, S., Hsiao, K.K., and Iadecola, C. (1997). Increased susceptibility to ischemic brain damage in transgenic mice overexpressing the amyloid precursor protein. J Neurosci 17, 7655-7661.
77. Zhang, X., Zhou, K., Wang, R., Cui, J., Lipton, S.A., Liao, F.F., Xu, H., and Zhang, Y.W. (2007). Hypoxia-inducible factor 1alpha (HIF-1alpha)-mediated hypoxia increases BACE1 expression and beta-amyloid generation. J Biol Chem 282, 10873-10880. doi: 10.1074/jbc.M608856200.
78. Zheng, L., Vinters, H.V., Mack, W.J., Zarow, C., Ellis, W.G., and Chui, H.C. (2013). Cerebral atherosclerosis is associated with cystic infarcts and microinfarcts but not Alzheimer pathologic changes. Stroke 44, 2835-2841. doi: 10.1161/strokeaha.113.001945.