Elusive alzheimer's disease: Can immune signatures help our understanding of this challenging disease? Part 2: New immune paradigm

Discovery Medicine

Volumn 15, Issue 80, 2013, Pages 33-42

  Fulop, Tamas ^a   Lacombe, Guy ^a   Cunnane, Stephen ^a   Le Page, Aurélie ^a   Dupuis, Gilles ^b   Frost, Eric H ^b   Bourgade Navarro, Karine ^a   Goldeck, David ^c   Larbi, Anis ^d   Pawelec, Graham ^c  

^a UNIVERSITÉ DE SHERBROOKE   (Canada)

^b UNIVERSITY OF SHERBROOKE   (Canada)

^c UNIVERSITY OF TÜBINGEN   (Germany)

^d AGENCY FOR SCIENCE   (Singapore)

Author keywords

[No Author keywords available]

Indexed keywords

AMYLOID BETA PROTEIN; BIOLOGICAL MARKER;

ALZHEIMER DISEASE; ANIMAL; BIOLOGICAL MODEL; HUMAN; IMMUNOLOGY; METABOLISM; REVIEW;

ALZHEIMER DISEASE; AMYLOID BETA-PEPTIDES; ANIMALS; BIOLOGICAL MARKERS; HUMANS; MODELS, BIOLOGICAL;

MLCS; MLOWN;

EID: 84881281872     PISSN: 15396509     EISSN: 19447930     Source Type: Journal    
DOI: None     Document Type: Article

References (99)

1. Aiello AE, Haan M, Blythe L, Moore K, Gonzalez JM, Jagust W. The influence of latent viral infection on rate of cognitive decline over 4 years. J Am Geriatr Soc 54(7):1046-1054, 2006.
2. Aisen PS, Davis KL. Inflammatory mechanisms in Alzheimer's disease: implications for therapy. Am J Psychiatry 151(8):1105-1113, 1994.
3. Ard MD, Cole GM, Wei J, Mehrle AP, Fratkin JD. Scavenging of Alzheimer's amyloid beta-protein by microglia in culture. J Neurosci Res 43(2):190-202, 1996.
4. Avagyan H, Goldenson B, Tse E, Masoumi A, Porter V, Wiedau-Pazos M, Sayre J, Ong R, Mahanian M, Koo P, Bae S, Micic M, Liu PT, Rosenthal MJ, Fiala M. Immune blood biomarkers of Alzheimer disease patients. J Neuroimmunol 210(1-2):67-72, 2009.
5. Blasko I, Grubeck-Loebenstein B. Role of the immune system in the pathogenesis, prevention and treatment of Alzheimer's disease. Drugs Aging 20(2):101-113, 2003.
6. Blasko I, Knaus G, Weiss E, Kemmler G, Winkler C, Falkensammer G, Griesmacher A, Wurzner R, Marksteiner J, Fuchs D. Cognitive deterioration in Alzheimer's disease is accompanied by increase of plasma neopterin. J Psychiatr Res 41(8):694-701, 2007.
7. Blasko I, Stampfer-Kountchev M, Robatscher P, Veerhuis R, Eikelenboom P, Grubeck-Loebenstein B. How chronic inflammation can affect the brain and support the development of Alzheimer's disease in old age: the role of microglia and astrocytes. Aging Cell 3(4):169-176, 2004.
8. Bonotis K, Krikki E, Holeva V, Aggouridaki C, Costa V, Baloyannis S. Systemic immune aberrations in Alzheimer's disease patients. J Neuroimmunol 193(1-2):183-187, 2008.
9. Britschgi M, Wyss-Coray T. Systemic and acquired immune responses in Alzheimer's disease. Int Rev Neurobiol 82:205-233, 2007.
10. Broussard GJ, Mytar J, Li RC, Klapstein GJ. The role of inflammatory processes in Alzheimer's disease. Inflammopharmacology 20(3):109-126, 2012.
11. Bruunsgaard H, Andersen-Ranberg K, Jeune B, Pedersen AN, Skinhøj P, Pedersen BK. A high plasma concentration of TNF-alpha is associated with dementia in centenarians. J Gerontol A Biol Sci Med Sci 54(7):M357-M364, 1999.
12. Butchart J, Holmes C. Systemic and central immunity in Alzheimer's disease: therapeutic implications. CNS Neurosci Ther 18(1):64-76, 2012.
13. Chidrawar S, Khan N, Wei W, McLarnon A, Smith N, Nayak L, Moss P. Cytomegalovirus-seropositivity has a profound influence on the magnitude of major lymphoid subsets within healthy individuals. Clin Exp Immunol 155(3):423-432, 2009.
14. Chen K, Iribarren P, Hu J, Chen J, Gong W, Cho EH, Lockett S, Dunlop NM, Wang JM. Activation of Toll-like receptor 2 on microglia promotes cell uptake of Alzheimer disease-associated amyloid beta peptide. J Biol Chem 281(6):3651-3659, 2006.
15. Colton CA, Gilbert DL. Production of superoxide anions by a CNS macrophage, the microglia. FEBS Lett 223(2):284-288, 1987.
16. Côté S, Carmichael PH, Verreault R, Lindsay J, Lefebvre J, Laurin D. Nonsteroidal anti-inflammatory drug use and the risk of cognitive impairment and Alzheimer's disease. Alzheimers Dement 8(3):219-226, 2012.
17. Cunnane S, Nugent S, Roy M, Courchesne-Loyer A, Croteau E, Tremblay S, Castellano A, Pifferi F, Bocti C, Paquet N, Begdouri H, Bentourkia M, Turcotte E, Allard M, Barberger-Gateau P, Fulop T, Rapoport SI. Brain fuel metabolism, aging, and Alzheimer's disease. Nutrition 27(1):3-20, 2011.
18. Derhovanessian E, Maier AB, Beck R, Jahn G, Hähnel K, Slagboom PE, de Craen AJ, Westendorp RG, Pawelec G. Hallmark features of immunosenescence are absent in familial longevity. J Immunol 185(8):4618-4624, 2010.
19. D'Mello C, Le T, Swain MG. Cerebral microglia recruit monocytes into the brain in response to tumor necrosis factor alpha signaling during peripheral organ inflammation. J Neurosci 29(7):2089-2102, 2009.
20. Dock JN, Effros RB. Role of CD8 T cell replicative senescence in human aging and in HIV-mediated immunosenescence. Aging Dis 2(5):382-397, 2011.
21. Douziech N, Seres I, Larbi A, Szikszay E, Roy PM, Arcand M, Dupuis G, Fulop T Jr. Modulation of human lymphocyte proliferative response with aging. Exp Gerontol 37(2-3):369-387, 2002.
22. Dunn N, Mullee M, Perry VH, Holmes C. Association between dementia and infectious disease: evidence from a case-control study. Alzheimer Dis Assoc Disord 19(2):91-94, 2005.
23. Engelhart MJ, Geerlings MI, Meijer J, Kiliaan A, Ruitenberg A, van Swieten JC, Stijnen T, Hofman A, Witteman JC, Breteler MM. Inflammatory proteins in plasma and the risk of dementia: the Rotterdam study. Arch Neurol 61(5):668-672, 2004.
24. Farina C, Aloisi F, Meinl E. Astrocytes are active players in cerebral innate immunity. Trends Immunol 28(3):138-145, 2007.
25. Feng Y, Li L, Sun XH. Monocytes and Alzheimer's disease. Neurosci Bull 27(2):115-122, 2011.
26. Fiala M, Lin J, Ringman J, Kermani-Arab V, Tsao G, Patel A, Lossinsky AS, Graves MC, Gustavson A, Sayre J, Sofroni E, Suarez T, Chiappelli F, Bernard G. Ineffective phagocytosis of amyloid-beta by macrophages of Alzheimer's disease patients. J Alzheimers Dis 7(3):221-232, 2005.
27. Fiala M, Liu PT, Espinosa-Jeffrey A, Rosenthal MJ, Bernard G, Ringman JM, Sayre J, Zhang L, Zaghi J, Dejbakhsh S, Chiang B, Hui J, Mahanian M, Baghaee A, Hong P, Cashman J. Innate immunity and transcription of MGAT-III and Toll-like receptors in Alzheimer's disease patients are improved by bisdemethoxycurcumin. Proc Natl Acad Sci U S A 104(31):12849-12854, 2007.
28. Foster JK, Verdile G, Bates KA, Martins RN. Immunization in Alzheimer's disease: naïve hope or realistic clinical potential? Mol Psychiatry 14(3):239-251, 2009.
29. Frautschy SA, Yang F, Irrizarry M, Hyman B, Saido TC, Hsiao K, Cole GM. Microglial response to amyloid plaques in APPsw transgenic mice. Am J Pathol 152(1):307-317, 1998.
30. Fulop T, Larbi A, Wikby A, Mocchegiani E, Hirokawa K, Pawelec G. Dysregulation of T-cell function in the elderly: scientific basis and clinical implications. Drugs Aging 22:589-603, 2005.
31. Fulop T, Lacombe G, Cunnane S, Le Page A, Dupuis G, Frost EH, Bourgade-Navarro K, Goldeck D, Larbi A, Pawelec G. Elusive Alzheimer's disease: Can immune signatures help our understanding of this challenging disease? Part 1: Clinical and historical background. Discov Med 15(80):23-32, 2013.
32. Fung A, Vizcaychipi M, Lloyd D, Wan Y, Ma D. Central nervous system inflammation in disease related conditions: mechanistic prospects. Brain Res 1446:144-155, 2012.
33. Gordon S. Alternative activation of macrophages. Nat Rev Immunol 3(1):23-35, 2003.
34. Guo P, Hirano M, Herrin BR, Li J, Yu C, Sadlonova A, Cooper MD. Dual nature of the adaptive immune system in lampreys. Nature 459:796-801, 2009.
35. Holmes C, Butchart J. Systemic inflammation and Alzheimer's disease. Biochem Soc Trans 39(4):898-901, 2011.
36. Holmes C, Cunningham C, Zotova E, Woolford J, Dean C, Kerr S, Culliford D, Perry VH. Systemic inflammation and disease progression in Alzheimer disease. Neurology 73(10):768-774, 2009.
37. Hoozemans JJ, Rozemuller AJ, van Haastert ES, Eikelenboom P, van Gool WA. Neuroinflammation in Alzheimer's disease wanes with age. J Neuroinflammation 8:171, 2011.
38. Itzhaki RF, Dobson CB, Shiplay SJ, Wozniak MA. The role of viruses and of APOE in dementia. Ann N Y Acad Sci 1019:15-18, 2004.
39. Khan KA, Coaquette A, Davrinche C, Herbein G. Bcl-3-regulated transcription from major immediate-early promoter of human cytomegalovirus in monocyte-derived macrophages. J Immunol 182(12):7784-7794, 2009.
40. Kipnis J, Avidan H, Caspi RR, Schwartz M. Dual effect of CD4+CD25+ regulatory T cells in neurodegeneration: a dialogue with microglia. Proc Natl Acad Sci U S A 101(Suppl 2):14663-14669, 2004.
41. Kipnis J, Derecki NC, Yang C, Scrable H. Immunity and cognition: what do age-related dementia, HIV-dementia and 'chemo-brain' have in common? Trends Immunol 29(10):455-463, 2008.
42. Koch S, Larbi A, Derhovanessian E, Ozcelik D, Naumova E, Pawelec G. Multiparameter flow cytometric analysis of CD4 and CD8 T cell subsets in young and old people. Immun Ageing 5:6, 2008.
43. Korn T, Bettelli E, Oukka M, Kuchroo VK. IL-17 and Th17 cells. Annu Rev Immunol 27:485-517, 2009.
44. Larbi A, Franceschi C, Mazzatti D, Solana R, Wikby A, Pawelec G. Aging of the immune system as a prognostic factor for human longevity.
45. Larbi A, Dupuis G, Khalil A, Douziech N, Fortin C, Fülöp T Jr. Differential role of lipid rafts in the functions of CD4+ and CD8+ human T lymphocytes with aging. Cell Signal 18(7):1017-1030, 2006.
46. Larbi A, Pawelec G, Witkowski JM, Schipper HM, Derhovanessian E, Goldeck D, Fulop T. Dramatic shifts in circulating CD4 but not CD8 T cell subsets in mild Alzheimer's disease. J Alzheimers Dis 17(1):91-103, 2009.
47. Li M, Shang DS, Zhao WD, Tian L, Li B, Fang WG, Zhu L, Man SM, Chen YH. Amyloid beta interaction with receptor for advanced glycation end products up-regulates brain endothelial CCR5 expression and promotes T cells crossing the blood-brain barrier. J Immunol 182(9):5778-5788, 2009.
48. Licastro F, Grimaldi LM, Bonafè M, Martina C, Olivieri F, Cavallone L, Giovanietti S, Masliah E, Franceschi C. Interleukin-6 gene alleles affect the risk of Alzheimer's disease and levels of the cytokine in blood and brain. Neurobiol Aging 24(7):921-926, 2003.
49. Liu S, Liu Y, Hao W, Wolf L, Kiliaan AJ, Penke B, Rübe CE, Walter J, Heneka MT, Hartmann T, Menger MD, Fassbender K. TLR2 is a primary receptor for Alzheimer's amyloid β peptide to trigger neuroinflammatory activation. J Immunol 188(3):1098-1107, 2012.
50. Lombardi VR, Garcia M, Rey L, Cacabelos R. Characterization of cytokine production, screening of lymphocyte subset patterns and in vitro apoptosis in healthy and Alzheimer's Disease (AD) individuals. J Neuroimmunol 97:163-171, 1999.
51. Lucin KM, Wyss-Coray T. Immune activation in brain aging and neurodegeneration: too much or too little? Neuron 64(1):110-122, 2009.
52. McElhaney JE, Zhou X, Talbot HK, Soethout E, Bleackley RC, Granville DJ, Pawelec G. The unmet need in the elderly: how immunosenescence, CMV infection, co-morbidities and frailty are a challenge for the development of more effective influenza vaccines. Vaccine 30(12):2060-2067, 2012.
53. Miscia S, Ciccocioppo F, Lanuti P, Velluto L, Bascelli A, Pierdomenico L, Genovesi D, Di Siena A, Santavenere E, Gambi F, Ausili-Cèfaro G, Grimley PM, Marchisio M, Gambi D. Abeta(1-42) stimulated T cells express P-PKC-delta and P-PKC-zeta in Alzheimer disease. Neurobiol Aging 30(3):394-406, 2009.
54. Mocchegiani E, Giacconi R, Cipriano R, Muti E, Gasparini N, Malavolta M. Are zinc-bound metallothionein isoforms (I+II and III) involved in impaired thymulin production and thymic involution during ageing? Immun Ageing 1(1):5-12, 2004.
55. Monsonego A, Zota V, Karni A, Krieger JI, Bar-Or A, Bitan G, Budson AE, Sperling R, Selkoe DJ, Weiner HL. Increased T cell reactivity to amyloid beta protein in older humans and patients with Alzheimer disease. J Clin Invest 112(3):415-422, 2003.
56. Ouyang Q, Wagner WM, Wikby A, Walter S, Aubert G, Dodi AI, Travers P, Pawelec G. Large numbers of dysfunctional CD8+ T lymphocytes bearing receptors for a single dominant CMV epitope in the very old. J Clin Immunol 23(4):247-257, 2003.
57. Panossian LA, Porter VR, Valenzuela HF, Zhu X, Reback E, Masterman D, Cummings JL, Effros RB. Telomere shortening in T cells correlates with Alzheimer's disease status. Neurobiol Aging 24:77-84, 2003.
58. Pawelec G. Immunity and ageing in man. Exp Gerontol 41(12):1239-1242, 2006.
59. Pawelec G, Akbar A, Caruso C, Solana R, Grubeck-Loebenstein B, Wikby A. Human immunosenescence: is it infectious? Immunol Rev 205:257-268, 2005.
60. Pellicanò M, Bulati M, Buffa S, Barbagallo M, Di Prima A, Misiano G, Picone P, Di Carlo M, Nuzzo D, Candore G, Vasto S, Lio D, Caruso C, Colonna-Romano G. Systemic immune responses in Alzheimer's disease: in vitro mononuclear cell activation and cytokine production. J Alzheimers Dis 21(1):181-192, 2010.
61. Pellicanò M, Larbi A, Goldeck D, Colonna-Romano G, Buffa S, Bulati M, Rubino G, Iemolo F, Candore G, Caruso C, Derhovanessian E, Pawelec G. Immune profiling of Alzheimer patients. J Neuroimmunol 242(1-2):52-59, 2012.
62. Pizza V, Agresta A, D'Acunto CW, Festa M, Capasso A. Neuroinflammation and ageing: current theories and an overview of the data. Rev Recent Clin Trials 6(3):189-203, 2011.
63. Querfurth HW, LaFerla FM. Alzheimer's disease. N Engl J Med 362(4):329-344, 2010.
64. Reale M, Iarlori C, Feliciani C, Gambi D. Peripheral chemokine receptors, their ligands, cytokines and Alzheimer's disease. J Alzheimers Dis 14(2):147-159, 2008.
65. Richard KL, Filali M, Préfontaine P, Rivest S. Toll-like receptor 2 acts as a natural innate immune receptor to clear amyloid beta 1-42 and delay the cognitive decline in a mouse model of Alzheimer's disease. J Neurosci 28(22):5784-5793, 2008.
66. Richartz-Salzburger E, Batra A, Stransky E, Laske C, Köhler N, Bartels M, Buchkremer G, Schott K. Altered lymphocyte distribution in Alzheimer's disease. J Psychiatr Res 41(1-2):174-178, 2007.
67. Rivest S. Regulation of innate immune responses in the brain. Nat Rev Immunol 9(6):429-439, 2009.
68. Rocha NP, Teixeira AL, Coelho FM, Caramelli P, Guimarães HC, Barbosa IG, da Silva TA, Mukhamedyarov MA, Zefirov AL, Rizvanov AA, Kiyasov AP, Vieira LB, Janka Z, Palotás A, Reis HJ. Peripheral blood mono-nuclear cells derived from Alzheimer's disease patients show elevated baseline levels of secreted cytokines but resist stimulation with β-amyloid peptide. Mol Cell Neurosci 49(1):77-84, 2012.
69. Rogers J, Luber-Narod J, Styren SD, Civin WH. Expression of immune system-associated antigens by cells of the human central nervous system: relationship to the pathology of Alzheimer's disease. Neurobiol Aging 9(4):339-349, 1988.
70. Rubio-Perez JM, Morillas-Ruiz JM. A review: inflammatory process in Alzheimer's disease, role of cytokines. ScientificWorldJournal 2012:756357, 2012.
71. Salminen A, Ojala J, Kauppinen A, Kaarniranta K, Suuronen T. Inflammation in Alzheimer's disease: amyloid-beta oligomers trigger innate immunity defence via pattern recognition receptors. Prog Neurobiol 87(3):181-194, 2009.
72. Schindowski K, Eckert A, Peters J, Gorriz C, Schramm U, Weinandi T, Maurer K, Frölich L, Müller WE. Increased T-cell reactivity and elevated levels of CD8+ memory T-cells in Alzheimer's disease-patients and T-cell hyporeactivity in an Alzheimer's disease-mouse model: implications for immunotherapy. Neuromolecular Med 9(4):340-54, 2007.
73. Schwartz M, Shechter R. Systemic inflammatory cells fight off neurodegenerative disease. Nat Rev Neurol 6(7):405-410, 2010.
74. Shaftel SS, Kirkanides S, Olschowka JR, Miller JN, Johnson RE, O'Banion MK. Sustained hippocampal IL-1 beta overexpression mediates chronic neuroinflammation and ameliorates Alzheimer plaque pathology. J Clin Invest 117:1595-1604, 2007.
75. Shalit F, Sredni B, Brodie C, Kott E, Huberman M. T lymphocyte subpopulations and activation markers correlate with severity of Alzheimer's disease. Clin Immunol Immunopathol 75:246-250, 1995.
76. Solana R, Tarazona R, Gayoso I, Lesur O, Dupuis G, Fulop T. Innate immunosenescence: effect of aging on cells and receptors of the innate immune system in humans. Semin Immunol 24(5):331-341, 2012.
77. Solt LA, Kumar N, Nuhant P, Wang Y, Lauer JL, Liu J, Istrate MA, Kamenecka TM, Roush WR, Vidović D, Schürer SC, Xu J, Wagoner G, Drew PD, Griffin PR, Burris TP. Suppression of TH17 differentiation and autoimmunity by a synthetic ROR ligand. Nature 472(7344):491-494, 2011.
78. Soulet D, Rivest S. Bone-marrow-derived microglia: myth or reality? Curr Opin Pharmacol 8(4):508-518, 2008.
79. Speciale L, Calabrese E, Saresella M, Tinelli C, Mariani C, Sanvito L, Longhi R, Ferrante P. Lymphocyte subset patterns and cytokine production in Alzheimer's disease patients. Neurobiol Aging 28(8):1163-1169, 2007.
80. Strandberg TE, Pitkala KH, Linnavuori K, Tilvis RS. Cognitive impairment and infectious burden in the elderly. Arch Gerontol Geriatr Suppl (9):419-423, 2004.
81. Swerdlow RH, Burns JM, Khan SM. The Alzheimer's disease mitochondrial cascade hypothesis. J Alzheimers Dis 20(Suppl 2):S265-S279, 2010.
82. Tahara K, Kim HD, Jin JJ, Maxwell JA, Li L, Fukuchi K. Role of toll-like receptor signalling in Abeta uptake and clearance. Brain 129(Pt 11):3006-3019, 2006.
83. Tan ZS, Beiser AS, Vasan RS, Roubenoff R, Dinarello CA, Harris TB, Benjamin EJ, Au R, Kiel DP, Wolf PA, Seshadri S. Inflammatory markers and the risk of Alzheimer disease: the Framingham Study. Neurology 68(22):1902-1908, 2007.
84. Tan J, Town T, Abdullah L, Wu Y, Placzek A, Small B, Kroeger J, Crawford F, Richards D, Mullan M. CD45 isoform alteration in CD4+ T cells as a potential diagnostic marker of Alzheimer's disease. J Neuroimmunol 132:164-172, 2002.
85. Tilvis RS, Kähönen-Väre MH, Jolkkonen J, Valvanne J, Pitkala KH, Strandberg TE. Predictors of cognitive decline and mortality of aged people over a 10-year period. J Gerontol A Biol Sci Med Sci 59(3):268-274, 2004.
86. Trieb K, Rasmayr G, Sgone R, Lassmann H, Grubeck-Loebenstein B. APP peptides stimulate lymphocyte proliferation in normals, but not in patients with Alzheimer's disease. Neurobiol Aging 17:541-547, 1996.
87. Togo T, Akiyama H, Iseki E, Kondo H, Ikeda K, Kato M, Oda T, Tsuchiya K, Kosaka K. Occurrence of T cells in the brain of Alzheimer's disease and other neurological diseases. J Neuroimmunol 124(1-2):83-92, 2002.
88. Town T, Tan J, Flavell RA, Mullan M. T-cells in Alzheimer's disease. Neuromolecular Med 7(3):255-264, 2005.
89. Tschape JA, Hartmann T. Therapeutic perspectives in Alzheimer's disease. Recent patents. CNS Drug Discov 1:119-127, 2006.
90. van den Heuvel C, Thornton E, Vink R. Traumatic brain injury and Alzheimer's disease: a review. Prog Brain Res 161:303-316, 2007.
91. Varin A, Mukhopadhyay S, Herbein G, Gordon S. Alternative activation of macrophages by IL-4 impairs phagocytosis of pathogens but potentiates microbial-induced signalling and cytokine secretion. Blood 115(2):353-362, 2010.
92. Vescovini R, Biasini C, Telera AR, Basaglia M, Stella A, Magalini F, Bucci L, Monti D, Lazzarotto T, Dal Monte P, Pedrazzoni M, Medici MC, Chezzi C, Franceschi C, Fagnoni FF, Sansoni P. Intense antiextracellular adaptive immune response to human cytomegalovirus in very old subjects with impaired health and cognitive and functional status. J Immunol 184(6):3242-3249, 2010.
93. Vlad SC, Miller DR, Kowall NW, Felson DT. Protective effects of NSAIDs on the development of Alzheimer disease. Neurology 70(19):1672-1677, 2008.
94. Weiner HL, Frenkel D. Immunology and immunotherapy of Alzheimer's disease. Nat Rev Immunol 6:404-416, 2006.
95. Wikby A, Ferguson F, Forsey R, Thompson J, Strindhal J, Lofgren S, Nilsson BO, Ernerudh J, Pawelec G, Johansson B. An immune risk phenotype, cognitive impairment, and survival in very late life: impact of allostatic load in Swedish octogenarian and nonagenarian humans. J Gerontol A Biol Sci Med Sci 60(5):556-565, 2005.
96. Woodhouse A, Dickson TC, Vickers JC. Vaccination strategies for Alzheimer's disease. Drugs Aging 24:107-119, 2007.
97. Yin Y, Wen S, Li G, Wang D. Hypoxia enhances stimulating effect of amyloid beta peptide (25-35) for interleukin 17 and T helper lymphocyte subtype 17 upregulation in cultured peripheral blood mononuclear cells. Microbiol Immunol 53:281-286, 2009.
98. Zaghi J, Goldenson B, Inayathullah M, Lossinsky AS, Masoumi A, Avagyan H, Mahanian M, Bernas M, Weinand M, Rosenthal MJ, Espinosa-Jeffrey A, de Vellis J, Teplow DB, Fiala M. Alzheimer disease macrophages shuttle amyloid-beta from neurons to vessels, contributing to amyloid angiopathy. Acta Neuropathol 117(2):111-124, 2009.
99. Zhu Y, Bickford PC, Sanberg P, Giunta B, Tan J. Blueberry opposes beta-amyloid peptide-induced microglial activation via inhibition of p44/42 mitogen-activation protein kinase. Rejuvenation Res 11(5):891-901, 2008.