Microglial dysfunction in brain aging and Alzheimer's disease

Biochemical Pharmacology

Volumn 88, Issue 4, 2014, Pages 594-604

  Mosher, Kira Irving ^a   Wyss Coray, Tony ^a,b  

^a STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b VA PALO ALTO HEALTH CARE SYSTEM   (United States)

Author keywords

Aging; Alzheimer's disease; Microglia; Neurodegeneration; Neuroinflammation

Indexed keywords

APOLIPOPROTEIN E; CD11B ANTIGEN; CD14 ANTIGEN; CD68 ANTIGEN; CHEMOKINE RECEPTOR CX3CR1; INTERLEUKIN 1BETA; INTERLEUKIN 6; TOLL LIKE RECEPTOR; TUMOR NECROSIS FACTOR ALPHA;

ALZHEIMER DISEASE; BLOOD BRAIN BARRIER; BRAIN DYSFUNCTION; CELL AGING; CELL COMMUNICATION; CELL MIGRATION; CELL MOTILITY; CELL PROLIFERATION; CYTOKINE PRODUCTION; GENETIC ASSOCIATION; HUMAN; IN VITRO STUDY; MICROGLIA; NERVE DEGENERATION; NERVOUS SYSTEM INFLAMMATION; NONHUMAN; OXIDATIVE STRESS; PATHOPHYSIOLOGY; PHAGOCYTOSIS; PHENOTYPE; PRIORITY JOURNAL; PROTEIN HOMEOSTASIS; REVIEW; RISK FACTOR; UPREGULATION;

AGING; ALZHEIMER'S DISEASE; MICROGLIA; NEURODEGENERATION; NEUROINFLAMMATION;

AGING; ALZHEIMER DISEASE; BRAIN; HUMANS; MICROGLIA;

EID: 84897954445     PISSN: 00062952     EISSN: 18732968     Source Type: Journal    
DOI: 10.1016/j.bcp.2014.01.008     Document Type: Review

References (153)

1. R. Stelzmann, H. Norman Schnitzlein, and F. Reed Murtagh An English translation of Alzheimer's 1907 paper, "Über eine eigenartige Erkankung der Hirnrinde" Clin Anat 8 6 1995 429 431
2. T. Samorajski How the human brain responds to aging J Am Geriatr Soc 24 1 1976 4 11
3. C. López-Otín, M.A. Blasco, L. Partridge, M. Serrano, and G. Kroemer The hallmarks of aging Cell 153 6 2013 1194 1217
4. U.-K. Hanisch, and H. Kettenmann Microglia: active sensor and versatile effector cells in the normal and pathologic brain Nat Neurosci 10 11 2007 1387 1394 (Pubitemid 350014685)
5. D. Davalos, J. Grutzendler, G. Yang, J.V. Kim, Y. Zuo, and S. Jung et al. ATP mediates rapid microglial response to local brain injury in vivo Nat Neurosci 8 6 2005 752 758 (Pubitemid 43085841)
6. A. Nimmerjahn, F. Kirchhoff, and F. Helmchen Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo Science 308 5726 2005 1314 1318 (Pubitemid 40746128)
7. C. Franceschi, M. Capri, D. Monti, S. Giunta, F. Olivieri, and F. Sevini et al. Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans Mech Ageing Dev 128 1 2007 92 105 (Pubitemid 46073065)
8. C. Cunningham, S. Campion, J. Teeling, L. Felton, and V.H. Perry The sickness behaviour and CNS inflammatory mediator profile induced by systemic challenge of mice with synthetic double-stranded RNA (poly I:C) Brain Behav Immun 21 4 2007 490 502 (Pubitemid 46528682)
9. D. Krstic, A. Madhusudan, J. Doehner, P. Vogel, T. Notter, and C. Imhof et al. Systemic immune challenges trigger and drive Alzheimer-like neuropathology in mice J Neuroinflammation 9 1 2012 1-1
10. V.H. Perry Contribution of systemic inflammation to chronic neurodegeneration Acta Neuropathol 120 3 2010 277 286
11. V.H. Perry, C. Cunningham, and C. Holmes Systemic infections and inflammation affect chronic neurodegeneration Nat Rev Immunol 7 2 2007 161 167 (Pubitemid 46174862)
12. D. Krstic, and I. Knuesel Deciphering the mechanism underlying late-onset Alzheimer disease Nat Rev Neurol 2012 1 10
13. C. Qiu, M. Kivipelto, and E. von Strauss Epidemiology of Alzheimer's disease: occurrence, determinants, and strategies toward intervention Dialogues Clin Neurosci 11 2 2009 111 128
14. E.B. Lee Obesity, leptin, and Alzheimer's disease Ann N Y Acad Sci 1243 1 2011 15 29
15. B. Misiak, J. Leszek, and A. Kiejna Metabolic syndrome, mild cognitive impairment and Alzheimer's disease - The emerging role of systemic low-grade inflammation and adiposity Brain Res Bull 89 3-4 2012 144 149
16. K.L. Puig, A.M. Floden, R. Adhikari, M.Y. Golovko, and C.K. Combs Amyloid precursor protein and proinflammatory changes are regulated in brain and adipose tissue in a murine model of high fat diet-induced obesity PLoS ONE 7 1 2012 e30378
17. L.B. Buckman, A.H. Hasty, D.K. Flaherty, C.T. Buckman, M.M. Thompson, and B.K. Matlock et al. Obesity induced by a high-fat diet is associated with increased immune cell entry into the central nervous system Brain Behav Immun 35 2013 33 42 C
18. J.-C. Lambert, C.A. Ibrahim-Verbaas, D. Harold, A.C. Naj, R. Sims, and C. Bellenguez et al. Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease Nat Genet 2013
19. A. Griciuc, A. Serrano-Pozo, R. Parrado Antonio, N. Lesinski Andrea, N. Asselin Caroline, and K. Mullin et al. Alzheimer's disease risk gene CD33 inhibits microglial uptake of amyloid beta Neuron 2013 1 13
20. P.R. Crocker, S.J. Mcmillan, and H.E. Richards CD33-related siglecs as potential modulators of inflammatory responses Ann N Y Acad Sci 1253 1 2012 102 111
21. L. Bertram, C. Lange, K. Mullin, M. Parkinson, M. Hsiao, and M.F. Hogan et al. Genome-wide association analysis reveals putative Alzheimer's disease susceptibility loci in addition to APOE Am J Hum Genet 83 5 2008 623 632
22. P. Hollingworth, D. Harold, R. Sims, A. Gerrish, J.-C. Lambert, and M.M. Carrasquillo et al. Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease Nat Genet 43 5 2011 429 435
23. A.C. Naj, G. Jun, G.W. Beecham, L.-S. Wang, B.N. Vardarajan, and J. Buros et al. Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's disease Nat Genet 43 5 2011 436 441
24. R. Guerreiro, A. Wojtas, J. Bras, M. Carrasquillo, E. Rogaeva, and E. Majounie et al. TREM2 variants in Alzheimer's disease N Engl J Med 368 2 2013 117 127
25. T. Jonsson, H. Stefansson, S. Steinberg, I. Jonsdottir, P.V. Jonsson, and J. Snaedal et al. Variant of TREM2 associated with the risk of Alzheimer's disease N Engl J Med 368 2 2013 107 116
26. B. Zhang, C. Gaiteri, L.-G. Bodea, Z. Wang, J. Mcelwee, and A. Podtelezhnikov Alexei et al. Integrated systems approach identifies genetic nodes and networks in late-onset Alzheimer's disease Cell 153 3 2013 707 720
27. H. Neumann, and M.J. Daly Variant TREM2 as risk factor for Alzheimer's disease N Engl J Med 368 2 2013 182 184
28. C.L. Hsieh, M. Koike, S.C. Spusta, E.C. Niemi, M. Yenari, and M.C. Nakamura et al. A role for TREM2 ligands in the phagocytosis of apoptotic neuronal cells by microglia J Neurochem 109 4 2009 1144 1156
29. A. Boutajangout, and T. Wisniewski The innate immune system in Alzheimer's disease Int J Cell Biol 2013 2013 576383
30. S. Frank, G.J. Burbach, M. Bonin, M. Walter, W. Streit, and I. Bechmann et al. TREM2 is upregulated in amyloid plaque-associated microglia in aged APP23 transgenic mice Glia 56 13 2008 1438 1447
31. H. Crehan, J. Hardy, and J. Pocock Microglia, Alzheimer's disease, and complement Int J Alzheimer's Dis 2012 3 2012 1 10
32. T. Wyss-Coray, and J. Rogers Inflammation in Alzheimer disease-a brief review of the basic science and clinical literature Cold Spring Harbor Perspect Med 2 1 2012 a006346
33. J.-C. Lambert, S. Heath, G. Even, D. Campion, K. Sleegers, and M. Hiltunen et al. Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer's disease Nat Publish Group 2009 1 7
34. M.K. O'bryan, H.W. Baker, J.R. Saunders, L. Kirszbaum, I.D. Walker, and P. Hudson et al. Human seminal clusterin (SP-40,40). Isolation and characterization J Clin Investigat 85 5 1990 1477 1486 (Pubitemid 20176441)
35. J. Ghiso, E. Matsubara, A. Koudinov, N.H. Choi-Miura, M. Tomita, and T. Wisniewski et al. The cerebrospinal-fluid soluble form of Alzheimer's amyloid beta is complexed to SP-40,40 (apolipoprotein J), an inhibitor of the complement membrane-attack complex Biochem J 293 Pt 1 1993 27 30 (Pubitemid 23223142)
36. N.H. Choi-Miura, Y. Ihara, K. Fukuchi, M. Takeda, Y. Nakano, and T. Tobe et al. SP-40,40 is a constituent of Alzheimer's amyloid Acta Neuropathol 83 3 1992 260 264
37. P.L. McGeer, T. Kawamata, and D.G. Walker Distribution of clusterin in Alzheimer brain tissue Brain Res 579 2 1992 337 341
38. E. Kida, N.H. Choi-Miura, and K.E. Wisniewski Deposition of apolipoproteins E and J in senile plaques is topographically determined in both Alzheimer's disease and Down's syndrome brain Brain Res 685 1-2 1995 211 216
39. Z. Xie, M.E. Harris-White, P.A. Wals, S.A. Frautschy, C.E. Finch, and T.E. Morgan et al. (clusterin) activates rodent microglia in vivo and in vitro J Neurochem 93 4 2005 1038 1046 (Pubitemid 40695763)
40. G.M. Cole, and M.D. Ard Influence of lipoproteins on microglial degradation of Alzheimer's amyloid beta-protein Microsc Res Tech 50 4 2000 316 324 (Pubitemid 30651172)
41. H. Crehan, J. Hardy, and J. Pocock Blockage of CR1 prevents activation of rodent microglia Neurobiol Dis 54 2013 139 149 C
42. J. Rogers, R. Li, D. Mastroeni, A. Grover, B. Leonard, and G. Ahern et al. Peripheral clearance of amyloid beta peptide by complement C3-dependent adherence to erythrocytes Neurobiol Aging 27 12 2006 1733 1739 (Pubitemid 44572574)
43. P. Forabosco, A. Ramasamy, D. Trabzuni, R. Walker, C. Smith, and J. Bras et al. Insights into TREM2 biology by network analysis of human brain gene expression data Neurobiol Aging 34 12 2013 2699 2714
44. D. Cribbs, N. Berchtold, V. Perreau, P. Coleman, J. Rogers, and A. Tenner et al. Extensive innate immune gene activation accompanies brain aging, increasing vulnerability to cognitive decline and neurodegeneration: a microarray study J Neuroinflammation 9 2012 179
45. L.J. Lawson, V.H. Perry, and S. Gordon Turnover of resident microglia in the normal adult mouse brain Neuroscience 48 2 1992 405 415
46. H. Xu, M. Chen, E.J. Mayer, J.V. Forrester, and A.D. Dick Turnover of resident retinal microglia in the normal adult mouse Glia 55 11 2007 1189 1198 (Pubitemid 47204210)
47. K. Hua, M.K. Schindler, J.A. Mcquail, M.E. Forbes, and D.R. Riddle Regionally distinct responses of microglia and glial progenitor cells to whole brain irradiation in adult and aging rats PLoS ONE 7 12 2012 e52728
48. J. Long, A. Kalehua, N. Muth, M. Calhoun, M. Jucker, and J. Hengemihle et al. Stereological analysis of astrocyte and microglia in aging mouse hippocampus Neurobiol Aging 19 5 1998 497 503 (Pubitemid 29065499)
49. D.W. Vaughan, and A. Peters Neuroglial cells in the cerebral cortex of rats from young adulthood to old age: an electron microscope study J Neurocytol 3 4 1974 405 429
50. M.-È. Tremblay, M.L. Zettel, J.R. Ison, P.D. Allen, and A.K. Majewska Effects of aging and sensory loss on glial cells in mouse visual and auditory cortices Glia 60 4 2012 541 558
51. M.R. Damani, L. Zhao, A.M. Fontainhas, J. Amaral, R.N. Fariss, and W.T. Wong Age-related alterations in the dynamic behavior of microglia Aging Cell 10 2 2011 263 276
52. B. Ajami, J.L. Bennett, C. Krieger, W. Tetzlaff, and F.M.V. Rossi Local self-renewal can sustain CNS microglia maintenance and function throughout adult life Nat Neurosci 10 12 2007 1538 1543 (Pubitemid 350175883)
53. F. Marques, J.C. Sousa, N. Sousa, and J.A. Palha Blood-brain-barriers in aging and in Alzheimer's disease Mol Neurodegener 8 1 2013 38
54. W.J. Streit, and Q.-S. Xue The Brain's aging immune system Aging Dis 1 3 2010 254 261
55. J. Conde, and W. Streit Effect of aging on the microglial response to peripheral nerve injury Neurobiol Aging 27 10 2006 1451
56. B.E. Flanary, N.W. Sammons, C. Nguyen, D. Walker, and W.J. Streit Evidence that aging and amyloid promote microglial cell senescence Rejuvenat Res 10 1 2007 61 74 (Pubitemid 46449433)
57. J.K. Hefendehl, J.J. Neher, R.B. Sühs, S. Kohsaka, A. Skodras, and M. Jucker Homeostatic and injury-induced microglia behavior in the aging brain Aging Cell 2013
58. D.J. Baker, T. Wijshake, T. Tchkonia, N.K. Lebrasseur, B.G. Childs, and B.v.d. Sluis et al. Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders Nature 2011 1 6
59. S.A. Villeda, J. Luo, K.I. Mosher, B. Zou, M. Britschgi, and G. Bieri et al. The ageing systemic milieu negatively regulates neurogenesis and cognitive function Nature 477 7362 2011 90 94
60. M.H. Sieweke, and J.E. Allen Beyond stem cells: Self-renewal of differentiated macrophages Science 342 6161 2013 1242974-1242974
61. W. Kamphuis, M. Orre, L. Kooijman, M. Dahmen, and E.M. Hol Differential cell proliferation in the cortex of the appsweps1de9 Alzheimer's disease mouse model Glia 60 4 2012 615 629
62. L. Bondolfi, M. Calhoun, F. Ermini, H.G. Kuhn, K.-H. Wiederhold, and L. Walker et al. Amyloid-associated neuron loss and gliogenesis in the neocortex of amyloid precursor protein transgenic mice J Neurosci 22 2 2002 515 522 (Pubitemid 34049090)
63. I. Luccarini, C. Grossi, C. Traini, A. Fiorentini, T.E. Dami, and F. Casamenti Aβ plaque-associated glial reaction as a determinant of apoptotic neuronal death and cortical gliogenesis: A study in APP mutant mice Neurosci Lett 506 1 2012 94 99
64. A. Serrano-Pozo, T. Gómez-Isla, J.H. Growdon, M.P. Frosch, and B.T. Hyman A phenotypic change but not proliferation underlies glial responses in Alzheimer disease Am J Pathol 182 6 2013 2332 2344
65. M.B. Jørgensen, B.R. Finsen, M.B. Jensen, B. Castellano, N.H. Diemer, and J. Zimmer Microglial and astroglial reactions to ischemic and kainic acid-induced lesions of the adult rat hippocampus Exp Neurol 120 1 1993 70 88 (Pubitemid 23114031)
66. R. Ladeby, M. Wirenfeldt, D. Garcia-Ovejero, C. Fenger, L. Dissing-Olesen, and I. Dalmau et al. Microglial cell population dynamics in the injured adult central nervous system Brain Res Brain Res Rev 48 2 2005 196 206 (Pubitemid 40585750)
67. S. Itagaki, P.L. McGeer, H. Akiyama, S. Zhu, and D. Selkoe Relationship of microglia and astrocytes to amyloid deposits of Alzheimer disease J Neuroimmunol 24 3 1989 173 182 (Pubitemid 19271472)
68. S.D. Styren, W.H. Civin, and J. Rogers Molecular, cellular, and pathologic characterization of HLA-DR immunoreactivity in normal elderly and Alzheimer's disease brain Exp Neurol 110 1 1990 93 104 (Pubitemid 20376005)
69. P.L. McGeer, S. Itagaki, H. Tago, and E.G. McGeer Reactive microglia in patients with senile dementia of the Alzheimer type are positive for the histocompatibility glycoprotein HLA-DR Neurosci Lett 79 1-2 1987 195 200 (Pubitemid 17144469)
70. W.J. Streit Microglia and Alzheimer's disease pathogenesis J Neurosci Res 77 1 2004 1 8 (Pubitemid 38850050)
71. A. Sierra, A.C. Gottfried-Blackmore, B.S. Mcewen, and K. Bulloch Microglia derived from aging mice exhibit an altered inflammatory profile Glia 55 4 2007 412 424
72. J. Koenigsknecht-Talboo, M. Meyer-Luehmann, M. Parsadanian, M. Garcia-Alloza, M.B. Finn, and B.T. Hyman et al. Rapid microglial response around amyloid pathology after systemic anti - a antibody administration in PDAPP mice J Neurosci 28 52 2008 14156 14164
73. M. Orre, W. Kamphuis, L.M. Osborn, J. Melief, L. Kooijman, and I. Huitinga et al. Acute isolation and transcriptome characterization of cortical astrocytes and microglia from young and aged mice Neurobiol Aging 2013 1 14
74. M.-È. Tremblay, R.L. Lowery, and A.K. Majewska Microglial interactions with synapses are modulated by visual experience PLoS Biol 8 11 2010 e1000527
75. H. Wake, A.J. Moorhouse, S. Jinno, S. Kohsaka, and J. Nabekura Resting microglia directly monitor the functional state of synapses in vivo and determine the fate of ischemic terminals J Neurosci 29 13 2009 3974 3980
76. R.C. Paolicelli, G. Bolasco, F. Pagani, L. Maggi, M. Scianni, and P. Panzanelli et al. Synaptic pruning by microglia is necessary for normal brain development Science 333 6048 2011 1456 1458
77. P. Schafer Dorothy, K. Lehrman Emily, G. Kautzman Amanda, R. Koyama, R. Mardinly Alan, and R. Yamasaki et al. Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner Neuron 74 4 2012 691 705
78. M. Meyer-Luehmann, T.L. Spires-Jones, C. Prada, M. Garcia-Alloza, A. De Calignon, and A. Rozkalne et al. Rapid appearance and local toxicity of amyloid-(plaques in a mouse model of Alzheimer's disease Nature 451 7179 2008 720 724 (Pubitemid 351220570)
79. J.B. Davis, H.F. McMurray, and D. Schubert The amyloid beta-protein of Alzheimer's disease is chemotactic for mononuclear phagocytes Biochem Biophys Res Commun 189 2 1992 1096 1100 (Pubitemid 23032488)
80. K. Maeda, M. Nakai, S. Maeda, T. Kawamata, T. Yamaguchi, and C. Tanaka Possible different mechanism between amyloid-beta (25-35)-and substance P-induced chemotaxis of murine microglia Gerontology 43Suppl.1 1997 11 15 (Pubitemid 27230643)
81. M.D. Ard, G.M. Cole, J. Wei, A.P. Mehrle, and J.D. Fratkin Scavenging of Alzheimer's amyloid beta-protein by microglia in culture J Neurosci Res 43 2 1996 190 202 (Pubitemid 26044233)
82. J.G. McLarnon Microglial chemotactic signaling factors in Alzheimer's disease Am J Neurodegener Dis 1 3 2012 199 204
83. J. Rogers, and L.F. Lue Microglial chemotaxis, activation, and phagocytosis of amyloid beta-peptide as linked phenomena in Alzheimer's disease Neurochem Int 39 5-6 2001 333 340 (Pubitemid 32907397)
84. J. El Khoury, M. Toft, S.E. Hickman, T.K. Means, K. Terada, and C. Geula et al. Ccr2 deficiency impairs microglial accumulation and accelerates progression of Alzheimer-like disease Nat Med 13 4 2007 432 438 (Pubitemid 46559828)
85. G. Naert, and S. Rivest CC Chemokine Receptor 2 deficiency aggravates cognitive impairments and amyloid pathology in a transgenic mouse model of Alzheimer's disease J Neurosci 31 16 2011 6208 6220
86. J.K. Ryu, T. Cho, H.B. Choi, Y.T. Wang, and J.G. Mclarnon Microglial VEGF receptor response is an integral chemotactic component in Alzheimer's disease pathology J Neurosci 29 1 2009 3 13
87. J.B. El Khoury, K.J. Moore, T.K. Means, J. Leung, K. Terada, and M. Toft et al. CD36 mediates the innate host response to beta-amyloid J Exp Med 197 12 2003 1657 1666 (Pubitemid 36745341)
88. S.L. Yates, L.H. Burgess, J. Kocsis-Angle, J.M. Antal, M.D. Dority, and P.B. Embury et al. Amyloid beta and amylin fibrils induce increases in proinflammatory cytokine and chemokine production by THP-1 cells and murine microglia J Neurochem 74 3 2000 1017 1025 (Pubitemid 30104297)
89. L.F. Lue, D.G. Walker, L. Brachova, T.G. Beach, J. Rogers, and A.M. Schmidt et al. Involvement of microglial receptor for advanced glycation endproducts (RAGE) in Alzheimer's disease: identification of a cellular activation mechanism Exp Neurol 171 1 2001 29 45 (Pubitemid 32848443)
90. S. Gordon, and F.O. Martinez Alternative activation of macrophages: mechanism and functions Immunity 32 5 2010 593 604
91. L. Sheffield, and N. Berman Microglial expression of MHC class II increases in normal aging of nonhuman primates Neurobiol Aging 19 1 1998 47
92. A. Wong, N. Patel, N. Patel, M. Wei, T. Morgan, and M. de Beer et al. Macrosialin increases during normal brain aging are attenuated by caloric restriction Neurosci Lett 390 2 2005 76 80 (Pubitemid 41415810)
93. M. Schindler, M. Forbes, M. Robbins, and D. Riddle Aging-dependent changes in the radiation response of the adult rat brain Int J Radiat Oncol Biol Phys 70 3 2008 826 834
94. A.D. Hart, A. Wyttenbach, V.H. Perry, and J.L. Teeling Age related changes in microglial phenotype vary between CNS regions: Grey versus white matter differences Brain Behav Immun 26 5 2012 754 765
95. G.J. Harry Microglia during development and aging Pharmacol Therap 139 3 2013 313 326
96. J.R. Conde, and W.J. Streit Microglia in the aging brain J Neuropathol Exp Neurol 65 3 2006 199 203
97. J. Rogers, J. Luber-Narod, S.D. Styren, and W.H. Civin 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 1988 339 349 (Pubitemid 19262065)
98. R. Strohmeyer, M. Ramirez, G.J. Cole, K. Mueller, and J. Rogers Association of factor H of the alternative pathway of complement with agrin and complement receptor 3 in the Alzheimer's disease brain J Neuroimmunol 131 1-2 2002 135 146
99. Y.M. Arends, C. Duyckaerts, J.M. Rozemuller, P. Eikelenboom, and J.J. Hauw Microglia, amyloid and dementia in Alzheimer disease. A correlative study Neurobiol Aging 21 1 2000 39 47 (Pubitemid 30224784)
100. P.L. Di Patre, S.L. Read, J.L. Cummings, U. Tomiyasu, L.M. Vartavarian, and D.L. Secor et al. Progression of clinical deterioration and pathological changes in patients with Alzheimer disease evaluated at biopsy and autopsy Arch Neurol 56 10 1999 1254 1261 (Pubitemid 29473218)
101. G.E. Landreth, and E.G. Reed-Geaghan Curr Top Microbiol Immunol 336 2009 137 153
102. B. Cameron, and G.E. Landreth Inflammation, microglia, and Alzheimer's disease Neurobiol Dis 37 3 2010 503 509
103. R. Von Bernhardi, J.E. Tichauer, and J. Eugenín Aging-dependent changes of microglial cells and their relevance for neurodegenerative disorders J Neurochem 112 5 2010 1099 1114
104. H. Nakanishi, and Z. Wu Microglia-aging: roles of microglial lysosome- and mitochondria-derived reactive oxygen species in brain aging Behav Brain Res 201 1 2009 1 7
105. S. Jimenez, D. Baglietto-Vargas, C. Caballero, I. Moreno-Gonzalez, M. Torres, and R. Sanchez-Varo et al. Inflammatory response in the hippocampus of PS1M146L/APP751SL mouse model of Alzheimer's Disease: Age-dependent switch in the microglial phenotype from alternative to classic J Neurosci 28 45 2008 11650 11661
106. A. Kumar, B.A. Stoica, B. Sabirzhanov, M.P. Burns, A.I. Faden, and D.J. Loane Traumatic brain injury in aged animals increases lesion size and chronically alters microglial/macrophage classical and alternative activation states Neurobiol Aging 34 5 2013 1397 1411
107. A.M. Fenn, C.J. Henry, Y. Huang, A. Dugan, and J.P. Godbout Lipopolysaccharide-induced interleukin (IL)-4 receptor-alpha expression and corresponding sensitivity to the M2 promoting effects of IL-4 are impaired in microglia of aged mice Brain Behav Immun 26 5 2012 766 777
108. C.J. Henry, Y. Huang, A.M. Wynne, and J.P. Godbout Peripheral lipopolysaccharide (LPS) challenge promotes microglial hyperactivity in aged mice that is associated with exaggerated induction of both pro-inflammatory IL-1β and anti-inflammatory IL-10 cytokines Brain Behav Immun 23 3 2009 309 317
109. Lee DC, Ruiz CR, Lebson L, Selenica M-LB, Rizer J, Jr JBH, et al. Aging enhances classical activation but mitigates alternative activation in the central nervous system. Neurobiol Aging 2013;34(6):1610-1620.
110. S. Lively, and L.C. Schlichter Age-related comparisons of evolution of the inflammatory response after intracerebral hemorrhage in rats Transl Stroke Res 3 S1 2012 132 146
111. J.M. Crain, M. Nikodemova, and J.J. Watters Microglia express distinct M1 and M2 phenotypic markers in the postnatal and adult central nervous system in male and female mice J Neurosci Res 91 9 2013 1143 1151
112. S.M. Ye, and R.W. Johnson Increased interleukin-6 expression by microglia from brain of aged mice J Neuroimmunol 93 1-2 1999 139 148 (Pubitemid 29051559)
113. E.G. Njie, E. Boelen, F.R. Stassen, H.W.M. Steinbusch, D.R. Borchelt, and W.J. Streit Ex vivo cultures of microglia from young and aged rodent brain reveal age-related changes in microglial function Neurobiol Aging 33 1 2012 195.e1-e12
114. A.Y. Lai, C.D. Dibal, G.A. Armitage, I.R. Winship, and K.G. Todd Distinct activation profiles in microglia of different ages: A systematic study in isolated embryonic to aged microglial cultures Neuroscience 2013 1 11
115. Z. Xie, T.E. Morgan, I. Rozovsky, and C.E. Finch Aging and glial responses to lipopolysaccharide in vitro: greater induction of IL-1 and IL-6, but smaller induction of neurotoxicity Exp Neurol 182 1 2003 135 141 (Pubitemid 36776256)
116. W.H. Yu, L. Go, B.A. Guinn, P.E. Fraser, D. Westaway, and J. McLaurin Phenotypic and functional changes in glial cells as a function of age Neurobiol Aging 23 1 2002 105 115 (Pubitemid 34066541)
117. C. Colton, R. Mott, H. Sharpe, Q. Xu, W. Van Nostrand, and M. Vitek Expression profiles for macrophage alternative activation genes in AD and in mouse models of AD J Neuroinflammation 3 1 2006 27
118. M.T. Heneka, M.P. Kummer, A. Stutz, A. Delekate, S. Schwartz, and A. Vieira-Saecker et al. NLRP3 is activated in Alzheimer's disease and contributes to pathology in APP/PS1 mice Nature 493 7434 2013 674 678
119. L. Meda, P. Baron, E. Prat, E. Scarpini, G. Scarlato, and M.A. Cassatella et al. Proinflammatory profile of cytokine production by human monocytes and murine microglia stimulated with beta-amyloid[25-35] J Neuroimmunol 93 1-2 1999 45 52 (Pubitemid 29051550)
120. A. Jekabsone, P.K. Mander, A. Tickler, M. Sharpe, and G.C. Brown Fibrillar beta-amyloid peptide Abeta1-40 activates microglial proliferation via stimulating TNF-alpha release and H2O2 derived from NADPH oxidase: a cell culture study J Neuroinflammation 3 2006 24
121. V.D. Bianca, S. Dusi, E. Bianchini, I. Dal Prà, and F. Rossi beta-amyloid activates the O-2 forming NADPH oxidase in microglia, monocytes, and neutrophils. A possible inflammatory mechanism of neuronal damage in Alzheimer's disease J Biol Chem 274 22 1999 15493 15499
122. A. Klegeris, D.G. Walker, and P.L. McGeer Activation of macrophages by Alzheimer beta amyloid peptide Biochem Biophys Res Commun 199 2 1994 984 991 (Pubitemid 24181759)
123. M.M. Varnum, and T. Ikezu The classification of microglial activation phenotypes on neurodegeneration and regeneration in Alzheimer's Disease Brain Arch Immunol Ther Exp 60 4 2012 251 266
124. B.L. Wilkinson, and G.E. Landreth The microglial NADPH oxidase complex as a source of oxidative stress in Alzheimer's disease J Neuroinflammation 3 2006 30
125. C.K. Lee, R. Weindruch, and T.A. Prolla Gene-expression profile of the ageing brain in mice Nat Genet 25 3 2000 294 297 (Pubitemid 30437315)
126. L. Qin, Y. Liu, J.-S. Hong, and F.T. Crews NADPH oxidase and aging drive microglial activation, oxidative stress, and dopaminergic neurodegeneration following systemic LPS administration Glia 61 6 2013 855 868
127. A.M. Wynne, C.J. Henry, Y. Huang, A. Cleland, and J.P. Godbout Protracted downregulation of CX3CR1 on microglia of aged mice after lipopolysaccharide challenge Brain Behav Immun 24 7 2010 1190 1201
128. A.D. Bachstetter, J.M. Morganti, J. Jernberg, A. Schlunk, S.H. Mitchell, and K.W. Brewster et al. Fractalkine and CX3CR1 regulate hippocampal neurogenesis in adult and aged rats NBA 32 11 2011 2030 2044
129. F.F. Cox, D. Carney, A.-M. Miller, and M.A. Lynch CD200 fusion protein decreases microglial activation in the hippocampus of aged rats Brain Behav Immun 26 5 2012 789 796
130. M. Frank, R. Barrientos, J. Biedenkapp, J. Rudy, L. Watkins, and S. Maier mRNA up-regulation of MHC II and pivotal pro-inflammatory genes in normal brain aging Neurobiol Aging 27 5 2006 717 722
131. S. Al-Ali, and S. Al-Hussain An ultrastructural study of the phagocytic activity of astrocytes in adult rat brain J Anatomy 188 Pt 2 1996 257
132. Z. Lu, M.R. Elliott, Y. Chen, J.T. Walsh, A.L. Klibanov, and K.S. Ravichandran et al. Phagocytic activity of neuronal progenitors regulates adult neurogenesis Nat Cell Biol 13 8 2011 1 9
133. A. Sierra, J.M. Encinas, J.J.P. Deudero, J.H. Chancey, G. Enikolopov, and L.S. Overstreet-Wadiche et al. Microglia shape adult hippocampal neurogenesis through apoptosis-coupled phagocytosis Cell Stem Cell 7 4 2010 483 495
134. S. Liu, Y. Liu, W. Hao, L. Wolf, A.J. Kiliaan, and B. Penke et al. TLR2 is a primary receptor for Alzheimer's amyloid β peptide To trigger neuroinflammatory activation J Immunol 188 3 2012 1098 1107
135. J.-P. Michaud, M. Halle, A. Lampron, P. Theriault, P. Prefontaine, and M. Filali et al. Toll-like receptor 4 stimulation with the detoxified ligand monophosphoryl lipid A improves Alzheimer's disease-related pathology Proc Natl Acad Sci 110 5 2013 1941 1946
136. Y. Liu, S. Walter, M. Stagi, D. Cherny, M. Letiembre, and W. Schulz-Schaeffer et al. LPS receptor (CD14): a receptor for phagocytosis of Alzheimer's amyloid peptide Brain 128 Pt 8 2005 1778 1789 (Pubitemid 41373649)
137. S. Du Yan, X. Chen, J. Fu, M. Chen, H. Zhu, and A. Roher et al. RAGE and amyloid-β peptide neurotoxicity in Alzheimer's disease Nature 382 6593 1996 685 691 (Pubitemid 26282167)
138. S.E. Hickman, E.K. Allison, and J. El Khoury Microglial dysfunction and defective β -amyloid clearance pathways in aging Alzheimer's disease mice J Neurosci 28 33 2008 8354 8360
139. J. El Khoury, S. Hickman, C. Thomas, L. Cao, S. Silverstein, and J. Loike Scavenger receptor-mediated adhesion of microglia to β-amyloid fibrils Nature 1996
140. M.R. D'Andrea, G.M. Cole, and M.D. Ard The microglial phagocytic role with specific plaque types in the Alzheimer disease brain Neurobiol Aging 25 5 2004 675 683 (Pubitemid 38686491)
141. E. Solito, and M. Sastre Microglia function in Alzheimer's disease Front Pharmacol 3 2012 1 10
142. G. Krabbe, A. Halle, V. Matyash, J.L. Rinnenthal, G.D. Eom, and U. Bernhardt et al. functional impairment of microglia coincides with beta-amyloid deposition in mice with Alzheimer-like pathology PLoS ONE 8 4 2013 e60921
143. A.M. Floden, and C.K. Combs Microglia demonstrate age-dependent interaction with amyloid-β fibrils J Alzheimers Dis 25 2 2011 279 293
144. R.C. Taylor, and A. Dillin Aging as an event of proteostasis collapse Cold Spring Harbor Perspect Biol 3 5 2011 a004440-a004440
145. S. Mandrekar, Q. Jiang, C.Y.D. Lee, J. Koenigsknecht-Talboo, D.M. Holtzman, and G.E. Landreth Microglia mediate the clearance of soluble a through fluid phase macropinocytosis J Neurosci 29 13 2009 4252 4262
146. J.S. Miners, N. Barua, P.G. Kehoe, S. Gill, and S. Love Aβ-degrading enzymes: potential for treatment of Alzheimer disease J Neuropathol Exp Neurol 70 11 2011 944 959
147. E. Shimizu, K. Kawahara, M. Kajizono, M. Sawada, and H. Nakayama IL-4-induced selective clearance of oligomeric beta-amyloid peptide(1-42) by rat primary type 2 microglia J Immunol 181 9 2008 6503 6513
148. W.Q. Qiu Insulin-degrading enzyme regulates extracellular levels of amyloid beta -protein by degradation J Biol Chem 273 49 1998 32730 32738 (Pubitemid 28557658)
149. S. Prokop, K.R. Miller, and F.L. Heppner Microglia actions in Alzheimer's disease Acta Neuropathol 2013
150. S.A. Grathwohl, R.E. Kälin, T. Bolmont, S. Prokop, G. Winkelmann, and S.A. Kaeser et al. Formation and maintenance of Alzheimer's disease β-amyloid plaques in the absence of microglia Nat Neurosci 2009 1 3
151. R. Radde, T. Bolmont, S.A. Kaeser, J. Coomaraswamy, D. Lindau, and L. Stoltze et al. Aβ42-driven cerebral amyloidosis in transgenic mice reveals early and robust pathology EMBO Rep 7 9 2006 940 946 (Pubitemid 44523975)
152. C. Sturchler-Pierrat, D. Abramowski, M. Duke, K.H. Wiederhold, C. Mistl, and S. Rothacher et al. Two amyloid precursor protein transgenic mouse models with Alzheimer disease-like pathology Proc Natl Acad Sci USA 94 24 1997 13287 13292 (Pubitemid 27518514)
153. K.M. Lucin, C.E. O'Brien, G. Bieri, E. Czirr, K.I. Mosher, and R.J. Abbey et al. Microglial Beclin 1 regulates retromer trafficking and phagocytosis and is impaired in Alzheimer's disease Neuron 79 5 2013 873 886