CoChat
Sign Up
Cited by 421Neuroinflammation and Neurodegeneration MechanismsAlzheimer's disease research and treatmentsNeurological Disease Mechanisms and Treatments

Microglia and Inflammation in Alzheimers Disease

Open access
Mandrekar-Colucci, Shweta, Landreth, Gary E.·2010·CNS & Neurological Disorders - Drug Targets
DOI 10.2174/187152710791012071PMC PMC3653290
Open this paper in CoChat — free account

Abstract

One hundred and fifty years have elapsed since the original discovery of the microglial cell by Virchow. While this cell type has been well studied, the role of microglia in the pathology of many central nervous system diseases still remains enigmatic. It is widely accepted that microglial-mediated inflammation contributes to the progression of Alzheimer's disease (AD); however, the precise mechanisms through which these cells contribute to AD-related inflammation remains to be elucidated. In the AD brain, microglial cells are found in close association with amyloid beta (Abeta) deposits. Histological examination of AD brains as well as cell culture studies have shown that the interaction of microglia with fibrillar Abeta leads to their phenotypic activation. The conversion of these cells into a classically 'activated' phenotype results in production of chemokines, neurotoxic cytokines and reactive oxygen and nitrogen species that are deleterious to the CNS. However, microglia also exert a neuroprotective role through their ability to phagocytose Abeta particles and clear soluble forms of Abeta. These cells have been documented to play integral roles in tissue repair and inflammation, and in recent years it has been appreciated that this cell type is capable of facilitating a more complex response to pathogens by changing their activation status. A variety of new findings indicate that their role in the central nervous system is far more complex than previously appreciated. In this review we discuss the role of microglia in the normal brain and their phenotypic heterogeneity and how this may play a role in AD-related pathophysiology. We touch on what is known about their ability to recognize and clear Abeta peptides as well as more controversial topics, including various activation states of microglia and the ability of peripheral macrophages or monocytes to infiltrate the brain.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.2174/187152710791012071

Cites

40 of 40 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 114

  1. [1]Cole SL Vassar R The Alzheimer’s disease beta-secretase enzyme, BACE1 Mol Neurodegener 2007 2 22 18005427 PMC2211305
  2. [2]Perlmutter LS Barron E Chui HC Morphologic association between microglia and senile plaque amyloid in Alzheimer’s disease Neurosci Lett 1990 119 1 32 36 2097581
  3. [4]Frackowiak J Wisniewski HM Wegiel J Merz GS Iqbal K Wang KC Ultrastructure of the microglia that phagocytose amyloid and the microglia that produce beta-amyloid fibrils Acta Neuropathol 1992 84 3 225 233 1414275
  4. [5]Wisniewski HM Barcikowska M Kida E Phagocytosis of beta/A4 amyloid fibrils of the neuritic neocortical plaques Acta Neuropathol 1991 81 5 588 590 1858487
  5. [6]Akiyama H Barger S Barnum S Bradt B Bauer J Cole GM Cooper NR Eikelenboom P Emmerling M Fiebich BL Finch CE Frautschy S Griffin WS Hampel H Hull M Landreth G Lue L Mrak R Mackenzie IR McGeer PL O’Banion MK Pachter J Pasinetti G Plata-Salaman C Rogers J Rydel R Shen Y Streit W Strohmeyer R Tooyoma I Van Muiswinkel FL Veerhuis R Walker D Webster S Wegrzyniak B Wenk G Wyss-Coray T Inflammation and Alzheimer’s disease Neurobiol Aging 2000 21 3 383 421 10858586 PMC3887148
  6. [7]Rezaie P Male D Mesoglia & microglia--a historical review of the concept of mononuclear phagocytes within the central nervous system J Hist Neurosci 2002 11 4 325 374 12557654
  7. [8]Morris L Graham CF Gordon S Macrophages in haemopoietic and other tissues of the developing mouse detected by the monoclonal antibody F4/80 Development 1991 112 2 517 526 1794320
  8. [9]Dheen ST Kaur C Ling EA Microglial activation and its implications in the brain diseases Curr Med Chem 2007 14 11 1189 1197 17504139
  9. [18]Wake H Moorhouse AJ Jinno S Kohsaka S Nabekura J Resting microglia directly monitor the functional state of synapses in vivo and determine the fate of ischemic terminals J Neurosci 2009 29 13 3974 3980 19339593 PMC6665392
  10. [19]Akiyama H Mori H Saido T Kondo H Ikeda K McGeer PL Occurrence of the diffuse amyloid beta-protein (Abeta) deposits with numerous Abeta-containing glial cells in the cerebral cortex of patients with Alzheimer’s disease Glia 1999 25 4 324 331 10028915
  11. [20]Mackenzie IR Hao C Munoz DG Role of microglia in senile plaque formation Neurobiol Aging 1995 16 5 797 804 8532113
  12. [23]Sasaki A Shoji M Harigaya Y Kawarabayashi T Ikeda M Naito M Matsubara E Abe K Nakazato Y Amyloid cored plaques in Tg2576 transgenic mice are characterized by giant plaques, slightly activated microglia, and the lack of paired helical filament-typed, dystrophic neurites Virchows Arch 2002 441 4 358 367 12404061
  13. [24]Wegiel J Imaki H Wang KC Wronska A Osuchowski M Rubenstein R Origin and turnover of microglial cells in fibrillar plaques of APPsw transgenic mice Acta Neuropathol 2003 105 4 393 402 12624793
  14. [25]Wegiel J Wang KC Imaki H Rubenstein R Wronska A Osuchowski M Lipinski WJ Walker LC LeVine H The role of microglial cells and astrocytes in fibrillar plaque evolution in transgenic APP(SW) mice Neurobiol Aging 2001 22 1 49 61 11164276
  15. [26]Stalder M Deller T Staufenbiel M Jucker M 3D-Reconstruction of microglia and amyloid in APP23 transgenic mice: no evidence of intracellular amyloid Neurobiol Aging 2001 22 3 427 434 11378249
  16. [27]Bornemann KD Wiederhold KH Pauli C Ermini F Stalder M Schnell L Sommer B Jucker M Staufenbiel M Abeta-induced inflammatory processes in microglia cells of APP23 transgenic mice Am J Pathol 2001 158 1 63 73 11141480 PMC1850262
  17. [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 1998 152 1 307 317 9422548 PMC1858113
  18. [30]Yan P Bero AW Cirrito JR Xiao Q Hu X Wang Y Gonzales E Holtzman DM Lee JM Characterizing the appearance and growth of amyloid plaques in APP/PS1 mice J Neurosci 2009 29 34 10706 10714 19710322 PMC2756291
  19. [32]Bolmont T Haiss F Eicke D Radde R Mathis CA Klunk WE Kohsaka S Jucker M Calhoun ME Dynamics of the microglial/amyloid interaction indicate a role in plaque maintenance J Neurosci 2008 28 16 4283 4292 18417708 PMC3844768
  20. [33]Maeda J Suhara T Zhang MR Okauchi T Yasuno F Ikoma Y Inaji M Nagai Y Takano A Obayashi S Suzuki K Novel peripheral benzodiazepine receptor ligand [11C]DAA1106 for PET: an imaging tool for glial cells in the brain Synapse 2004 52 4 283 291 15103694
  21. [34]Cagnin A Brooks DJ Kennedy AM Gunn RN Myers R Turkheimer FE Jones T Banati RB In-vivo measurement of activated microglia in dementia Lancet 2001 358 9280 461 467 11513911
  22. [35]Mankowski JL Queen SE Tarwater PJ Adams RJ Guilarte TR Elevated peripheral benzodiazepine receptor expression in simian immunodeficiency virus encephalitis J Neurovirol 2003 9 1 94 100 12587072
  23. [37]Versijpt JJ Dumont F Van Laere KJ Decoo D Santens P Audenaert K Achten E Slegers G Dierckx RA Korf J Assessment of neuroinflammation and microglial activation in Alzheimer’s disease with radiolabelled PK11195 and single photon emission computed tomography. A pilot study Eur Neurol 2003 50 1 39 47 12824711
  24. [39]Wiley CA Lopresti BJ Venneti S Price J Klunk WE DeKosky ST Mathis CA Carbon 11-labeled Pittsburgh Compound B and carbon 11-labeled (R)-PK11195 positron emission tomographic imaging in Alzheimer disease Arch Neurol 2009 66 1 60 67 19139300 PMC2666881
  25. [41]D’Mello C Le T Swain MG Cerebral microglia recruit monocytes into the brain in response to tumor necrosis factoralpha signaling during peripheral organ inflammation J Neurosci 2009 29 7 2089 2102 19228962 PMC6666330
  26. [42]Patel NS Paris D Mathura V Quadros AN Crawford FC Mullan MJ Inflammatory cytokine levels correlate with amyloid load in transgenic mouse models of Alzheimer’s disease J Neuroinflamm 2005 2 1 9 PMC555557 15762998
  27. [43]Herber DL Mercer M Roth LM Symmonds K Maloney J Wilson N Freeman MJ Morgan D Gordon MN Microglial activation is required for Abeta clearance after intracranial injection of lipopolysaccharide in APP transgenic mice J Neuroimmune Pharmacol 2007 2 2 222 231 18040847
  28. [44]Heneka MT O’Banion MK Inflammatory processes in Alzheimer’s disease J Neuroimmunol 2007 184 1–2 69 91 17222916
  29. [46]Hoozemans JJ Veerhuis R Rozemuller JM Eikelenboom P Neuroinflammation and regeneration in the early stages of Alzheimer’s disease pathology Int J Dev Neurosci 2006 24 2–3 157 165 16384684
  30. [47]Wyss-Coray T Inflammation in Alzheimer disease: driving force, bystander or beneficial response? Nat Med 2006 12 9 1005 1015 16960575
  31. [48]Lucin KM Wyss-Coray T Immune activation in brain aging and neurodegeneration: too much or too little? Neuron 2009 64 1 110 122 19840553 PMC2834890
  32. [50]Smits HA Rijsmus A van Loon JH Wat JW Verhoef J Boven LA Nottet HS Amyloid-beta-induced chemokine production in primary human macrophages and astrocytes J Neuroimmunol 2002 127 1–2 160 168 12044988
  33. [51]El Khoury JB Moore KJ Means TK Leung J Terada K Toft M Freeman MW Luster AD CD36 mediates the innate host response to beta-amyloid J Exp Med 2003 197 12 1657 1666 12796468 PMC2193948
  34. [52]Lue LF Brachova L Civin WH Rogers J Inflammation, A beta deposition, and neurofibrillary tangle formation as correlates of Alzheimer’s disease neurodegeneration J Neuropathol Exp Neurol 1996 55 10 1083 1088 8858005
  35. [56]Chakrabarty P Jansen-West K Beccard A Ceballos-Diaz C Levites Y Verbeeck C Zubair AC Dickson D Golde TE Das P Massive gliosis induced by interleukin-6 suppresses A{beta} deposition in vivo: evidence against inflammation as a driving force for amyloid deposition FASEB J 2009 24 2 548 559 19825975 PMC3083918
  36. [57]Ransohoff RM The MHP36 line of murine neural stem cells expresses functional CXCR1 chemokine receptors that initiate chemotaxis in vitro J Neuroimmunol 2007 186 1–2 199 17482680
  37. [58]Duan RS Yang X Chen ZG Lu MO Morris C Winblad B Zhu J Decreased fractalkine and increased IP-10 expression in aged brain of APP(swe) transgenic mice Neurochem Res 2008 33 6 1085 1089 18095157
  38. [59]Walker DG Dalsing-Hernandez JE Campbell NA Lue LF Decreased expression of CD200 and CD200 receptor in Alzheimer’s disease: a potential mechanism leading to chronic inflammation Exp Neurol 2009 215 1 5 19 18938162 PMC2765462
  39. [61]Mott RT Ait-Ghezala G Town T Mori T Vendrame M Zeng J Ehrhart J Mullan M Tan J Neuronal expression of CD22: novel mechanism for inhibiting microglial proinflammatory cytokine production Glia 2004 46 4 369 379 15095367
  40. [62]Hsieh CL Koike M Spusta SC Niemi EC Yenari M Nakamura MC Seaman WE A role for TREM2 ligands in the phagocytosis of apoptotic neuronal cells by microglia J Neurochem 2009 109 4 1144 1156 19302484 PMC3087597
  41. [63]Frank S Burbach GJ Bonin M Walter M Streit W Bechmann I Deller T TREM2 is upregulated in amyloid plaque-associated microglia in aged APP23 transgenic mice Glia 2008 56 13 1438 1447 18551625
  42. [64]Matozaki T Murata Y Okazawa H Ohnishi H Functions and molecular mechanisms of the CD47-SIRPalpha signalling pathway Trends Cell Biol 2009 19 2 72 80 19144521
  43. [65]Tan J Town T Paris D Mori T Suo Z Crawford F Mattson MP Flavell RA Mullan M Microglial activation resulting from CD40-CD40L interaction after beta-amyloid stimulation Science 1999 286 5448 2352 2355 10600748
  44. [66]Calingasan NY Erdely HA Altar CA Identification of CD40 ligand in Alzheimer’s disease and in animal models of Alzheimer’s disease and brain injury Neurobiol Aging 2002 23 1 31 39 11755016
  45. [67]Togo T Akiyama H Kondo H Ikeda K Kato M Iseki E Kosaka K Expression of CD40 in the brain of Alzheimer’s disease and other neurological diseases Brain Res 2000 885 1 117 121 11121537
  46. [68]Tan J Town T Crawford F Mori T DelleDonne A Crescentini R Obregon D Flavell RA Mullan MJ Role of CD40 ligand in amyloidosis in transgenic Alzheimer’s mice Nat Neurosci 2002 5 12 1288 1293 12402041
  47. [69]Mandrekar S Jiang Q Lee CY Koenigsknecht-Talboo J Holtzman DM Landreth GE Microglia mediate the clearance of soluble Abeta through fluid phase macropinocytosis J Neurosci 2009 29 13 4252 4262 19339619 PMC3034143
  48. [70]Koenigsknecht J Landreth G Microglial phagocytosis of fibrillar beta-amyloid through a beta1 integrin-dependent mechanism J Neurosci 2004 24 44 9838 9846 15525768 PMC6730228
  49. [71]Bamberger ME Harris ME McDonald DR Husemann J Landreth GE A cell surface receptor complex for fibrillar beta-amyloid mediates microglial activation J Neurosci 2003 23 7 2665 2674 12684452 PMC6742111
  50. [72]Paresce DM Chung HY Maxfield FR Slow degradation of aggregates of the Alzheimer’s disease amyloid beta-protein by microglial cells J Biol Chem 1997 272 46 29390 29397 9361021
  51. [73]Chung H Brazil MI Soe TT Maxfield FR Uptake, degradation, and release of fibrillar and soluble forms of Alzheimer’s amyloid beta-peptide by microglial cells J Biol Chem 1999 274 45 32301 32308 10542270
  52. [75]Koenigsknecht-Talboo J Landreth GE Microglial phagocytosis induced by fibrillar beta-amyloid and IgGs are differentially regulated by proinflammatory cytokines J Neurosci 2005 25 36 8240 8249 16148231 PMC6725530
  53. [76]Zelcer N Khanlou N Clare R Jiang Q Reed-Geaghan EG Landreth GE Vinters HV Tontonoz P Attenuation of neuroinflammation and Alzheimer’s disease pathology by liver x receptors Proc Natl Acad Sci USA 2007 104 25 10601 10606 17563384 PMC1890560
  54. [78]Wisniewski T Konietzko U Amyloid-beta immunisation for Alzheimer’s disease Lancet Neurol 2008 7 9 805 811 18667360 PMC2752661
  55. [79]Combs CK Bates P Karlo JC Landreth GE Regulation of beta-amyloid stimulated proinflammatory responses by peroxisome proliferator-activated receptor alpha Neurochem Int 2001 39 5–6 449 457 11578780
  56. [80]Shie FS Breyer RM Montine TJ Microglia lacking E Prostanoid Receptor subtype 2 have enhanced Abeta phagocytosis yet lack Abeta-activated neurotoxicity Am J Pathol 2005 166 4 1163 1172 15793296 PMC1602400
  57. [81]Liang X Wang Q Hand T Wu L Breyer RM Montine TJ Andreasson K Deletion of the prostaglandin E2 EP2 receptor reduces oxidative damage and amyloid burden in a model of Alzheimer’s disease J Neurosci 2005 25 44 10180 10187 16267225 PMC6725803
  58. [82]McGeer PL Schulzer M McGeer EG Arthritis and anti-inflammatory agents as possible protective factors for Alzheimer’s disease: a review of 17 epidemiologic studies Neurology 1996 47 2 425 432 8757015
  59. [83]Vlad SC Miller DR Kowall NW Felson DT Protective effects of NSAIDs on the development of Alzheimer disease Neurology 2008 70 19 1672 1677 18458226 PMC2758242
  60. [84]Lim GP Yang F Chu T Chen P Beech W Teter B Tran T Ubeda O Ashe KH Frautschy SA Cole GM Ibuprofen suppresses plaque pathology and inflammation in a mouse model for Alzheimer’s disease J Neurosci 2000 20 15 5709 5714 10908610 PMC6772529
  61. [85]Lim GP Yang F Chu T Gahtan E Ubeda O Beech W Overmier JB Hsiao-Ashec K Frautschy SA Cole GM Ibuprofen effects on Alzheimer pathology and open field activity in APPsw transgenic mice Neurobiol Aging 2001 22 6 983 991 11755007
  62. [86]McKee AC Carreras I Hossain L Ryu H Klein WL Oddo S LaFerla FM Jenkins BG Kowall NW Dedeoglu A Ibuprofen reduces Abeta, hyperphosphorylated tau and memory deficits in Alzheimer mice Brain Res 2008 1207 225 236 18374906 PMC2587244
  63. [87]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 2009 87 3 181 194 19388207
  64. [88]Cui Y Le Y Yazawa H Gong W Wang JM Potential role of the formyl peptide receptor-like 1 (FPRL1) in inflammatory aspects of Alzheimer’s disease J Leukoc Biol 2002 72 4 628 635 12377930
  65. [89]Cameron B Landreth GE Inflammation, microglia, and alzheimer’s disease Neurobiol Dis 2009 In Press PMC2823849 19833208
  66. [90]Combs CK Karlo JC Kao SC Landreth GE β-Amyloid stimulation of microglia and monocytes results in TNFalpha-dependent expression of inducible nitric oxide synthase and neuronal apoptosis J Neurosci 2001 21 4 1179 1188 11160388 PMC6762255
  67. [91]Combs CK Johnson DE Cannady SB Lehman TM Landreth GE Identification of microglial signal transduction pathways mediating a neurotoxic response to amyloidogenic fragments of beta-amyloid and prion proteins J Neurosci 1999 19 3 928 939 9920656 PMC6782151
  68. [93]Reed-Geaghan EG Savage JC Hise AG Landreth GE CD14 and toll-like receptors 2 and 4 are required for fibrillar A{beta}-stimulated microglial activation J Neurosci 2009 29 38 11982 11992 19776284 PMC2778845
  69. [94]Kawai T Akira S TLR signaling Semin Immunol 2007 19 1 24 32 17275323
  70. [96]Bsibsi M Ravid R Gveric D van Noort JM Broad expression of Toll-like receptors in the human central nervous system J Neuropathol Exp Neurol 2002 61 11 1013 1021 12430718
  71. [98]Fassbender K Walter S Kuhl S Landmann R Ishii K Bertsch T Stalder AK Muehlhauser F Liu Y Ulmer AJ Rivest S Lentschat A Gulbins E Jucker M Staufenbiel M Brechtel K Walter J Multhaup G Penke B Adachi Y Hartmann T Beyreuther K The LPS receptor (CD14) links innate immunity with Alzheimer’s disease FASEB J 2004 18 1 203 205 14597556
  72. [99]Liu Y Walter S Stagi M Cherny D Letiembre M Schulz-Schaeffer W Heine H Penke B Neumann H Fassbender K LPS receptor (CD14): a receptor for phagocytosis of Alzheimer’s amyloid peptide Brain 2005 128 Pt 8 1778 1789 15857927
  73. [100]Walter S Letiembre M Liu Y Heine H Penke B Hao W Bode B Manietta N Walter J Schulz-Schuffer W Fassbender K Role of the toll-like receptor 4 in neuroinflammation in Alzheimer’s disease Cell Physiol Biochem 2007 20 6 947 956 17982277
  74. [101]Tahara K Kim HD Jin JJ Maxwell JA Li L Fukuchi K Role of toll-like receptor signalling in Abeta uptake and clearance Brain 2006 129 Pt 11 3006 3019 16984903 PMC2445613
  75. [104]Richard KL Filali M Prefontaine 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 2008 28 22 5784 5793 18509040 PMC6670789
  76. [105]Krieg AM Therapeutic potential of Toll-like receptor 9 activation Nat Rev Drug Discov 2006 5 6 471 484 16763660
  77. [106]Ribes S Ebert S Czesnik D Regen T Zeug A Bukowski S Mildner A Eiffert H Hanisch UK Hammerschmidt S Nau R Toll-like receptor prestimulation increases phagocytosis of Escherichia coli DH5alpha and Escherichia coli K1 strains by murine microglial cells Infect Immun 2009 77 1 557 564 18981243 PMC2612236
  78. [107]Scholtzova H Kascsak RJ Bates KA Boutajangout A Kerr DJ Meeker HC Mehta PD Spinner DS Wisniewski T Induction of toll-like receptor 9 signaling as a method for ameliorating Alzheimer’s disease-related pathology J Neurosci 2009 29 6 1846 1854 19211891 PMC2699573
  79. [108]Kolev MV Ruseva MM Harris CL Morgan BP Donev RM Implication of complement system and its regulators in Alzheimer’s disease Curr Neuropharmacol 2009 7 1 1 8 19721814 PMC2724661
  80. [109]Stoltzner SE Grenfell TJ Mori C Wisniewski KE Wisniewski TM Selkoe DJ Lemere CA Temporal accrual of complement proteins in amyloid plaques in Down’s syndrome with Alzheimer’s disease Am J Pathol 2000 156 2 489 499 10666378 PMC1850044
  81. [110]Strohmeyer R Shen Y Rogers J Detection of complement alternative pathway mRNA and proteins in the Alzheimer’s disease brain Brain Res Mol Brain Res 2000 81 1–2 7 18 11000474
  82. [112]Rogers J Cooper NR Webster S Schultz J McGeer PL Styren SD Civin WH Brachova L Bradt B Ward P Complement activation by beta-amyloid in Alzheimer disease Proc Natl Acad Sci USA 1992 89 21 10016 10020 1438191 PMC50268
  83. [113]Bradt BM Kolb WP Cooper NR Complement-dependent proinflammatory properties of the Alzheimer’s disease beta-peptide J Exp Med 1998 188 3 431 438 9687521 PMC2212467
  84. [114]Wyss-Coray T Yan F Lin AH Lambris JD Alexander JJ Quigg RJ Masliah E Prominent neurodegeneration and increased plaque formation in complement-inhibited Alzheimer’s mice Proc Natl Acad Sci USA 2002 99 16 10837 10842 12119423 PMC125059
  85. [115]Maier M Peng Y Jiang L Seabrook TJ Carroll MC Lemere CA Complement C3 deficiency leads to accelerated amyloid beta plaque deposition and neurodegeneration and modulation of the microglia/macrophage phenotype in amyloid precursor protein transgenic mice J Neurosci 2008 28 25 6333 6341 18562603 PMC3329761
  86. [117]Fonseca MI Ager RR Chu SH Yazan O Sanderson SD LaFerla FM Taylor SM Woodruff TM Tenner AJ Treatment with a C5aR antagonist decreases pathology and enhances behavioral performance in murine models of Alzheimer’s disease J Immunol 2009 183 2 1375 1383 19561098 PMC4067320
  87. [118]Monk PN Scola AM Madala P Fairlie DP Function, structure and therapeutic potential of complement C5a receptors Br J Pharmacol 2007 152 4 429 448 17603557 PMC2050825
  88. [119]Nolte C Moller T Walter T Kettenmann H Complement 5a controls motility of murine microglial cells in vitro via activation of an inhibitory G-protein and the rearrangement of the actin cytoskeleton Neuroscience 1996 73 4 1091 1107 8809827
  89. [121]Martinez FO Helming L Gordon S Alternative activation of macrophages: an immunologic functional perspective Annu Rev Immunol 2009 27 451 483 19105661
  90. [123]Town T Nikolic V Tan J The microglial “activation” continuum: from innate to adaptive responses J Neuroinflamm 2005 2 24 PMC1298325 16259628
  91. [124]Morgan D Gordon MN Tan J Wilcock D Rojiani AM Dynamic complexity of the microglial activation response in transgenic models of amyloid deposition: implications for Alzheimer therapeutics J Neuropathol Exp Neurol 2005 64 9 743 753 16141783
  92. [125]Colton CA Mott RT Sharpe H Xu Q Van Nostrand WE Vitek MP Expression profiles for macrophage alternative activation genes in AD and in mouse models of AD J Neuroinflamm 2006 3 27 PMC1609108 17005052
  93. [127]Gratchev A Kzhyshkowska J Kothe K Muller-Molinet I Kannookadan S Utikal J Goerdt S Mphi1 and Mphi2 can be re-polarized by Th2 or Th1 cytokines, respectively, and respond to exogenous danger signals Immunobiology 2006 211 6–8 473 486 16920487
  94. [129]Loane DJ Deighan BF Clarke RM Griffin RJ Lynch AM Lynch MA Interleukin-4 mediates the neuroprotective effects of rosiglitazone in the aged brain Neurobiol Aging 2009 30 6 920 931 17950491
  95. [130]Gallardo-Soler A Gomez-Nieto C Campo ML Marathe C Tontonoz P Castrillo A Corraliza I Arginase I induction by modified lipoproteins in macrophages: a peroxisome proliferator-activated receptor-gamma/delta-mediated effect that links lipid metabolism and immunity Mol Endocrinol 2008 22 6 1394 1402 18323470 PMC5419540
  96. [131]van Rossum D Hilbert S Strassenburg S Hanisch UK Bruck W Myelin-phagocytosing macrophages in isolated sciatic and optic nerves reveal a unique reactive phenotype Glia 2008 56 3 271 283 18069669
  97. [133]Barron KD The microglial cell. A historical review J Neurol Sci 1995 134 Suppl 57 68 8847546
  98. [134]Malm TM Koistinaho M Parepalo M Vatanen T Ooka A Karlsson S Koistinaho J Bone-marrow-derived cells contribute to the recruitment of microglial cells in response to beta-amyloid deposition in APP/PS1 double transgenic Alzheimer mice Neurobiol Dis 2005 18 1 134 142 15649704
  99. [135]Simard AR Soulet D Gowing G Julien JP Rivest S Bone marrow-derived microglia play a critical role in restricting senile plaque formation in Alzheimer’s disease Neuron 2006 49 4 489 502 16476660
  100. [136]Stalder AK Ermini F Bondolfi L Krenger W Burbach GJ Deller T Coomaraswamy J Staufenbiel M Landmann R Jucker M Invasion of hematopoietic cells into the brain of amyloid precursor protein transgenic mice J Neurosci 2005 25 48 11125 11132 16319312 PMC6725647
  101. [137]Ajami B Bennett JL Krieger C Tetzlaff W Rossi FM Local self-renewal can sustain CNS microglia maintenance and function throughout adult life Nat Neurosci 2007 10 12 1538 1543 18026097
  102. [139]Calvo CF Yoshimura T Gelman M Mallat M Production of monocyte chemotactic protein-1 by rat brain macrophages Eur J Neurosci 1996 8 8 1725 1734 8921263
  103. [140]Glabinski AR Balasingam V Tani M Kunkel SL Strieter RM Yong VW Ransohoff RM Chemokine monocyte chemoattractant protein-1 is expressed by astrocytes after mechanical injury to the brain J Immunol 1996 156 11 4363 4368 8666808
  104. [141]El Khoury J Toft M Hickman SE Means TK Terada K Geula C Luster AD Ccr2 deficiency impairs microglial accumulation and accelerates progression of Alzheimer-like disease Nat Med 2007 13 4 432 438 17351623
  105. [142]Ishizuka K Kimura T Igata-yi R Katsuragi S Takamatsu J Miyakawa T Identification of monocyte chemoattractant protein-1 in senile plaques and reactive microglia of Alzheimer’s disease Psychiatry Clin Neurosci 1997 51 3 135 138 9225377
  106. [143]Izikson L Klein RS Charo IF Weiner HL Luster AD Resistance to experimental autoimmune encephalomyelitis in mice lacking the CC chemokine receptor (CCR)2 J Exp Med 2000 192 7 1075 1080 11015448 PMC2193310
  107. [144]Babcock AA Kuziel WA Rivest S Owens T Chemokine expression by glial cells directs leukocytes to sites of axonal injury in the CNS J Neurosci 2003 23 21 7922 7930 12944523 PMC6740601
  108. [146]Kiyota T Yamamoto M Xiong H Lambert MP Klein WL Gendelman HE Ransohoff RM Ikezu T CCL2 accelerates microglia-mediated Abeta oligomer formation and progression of neurocognitive dysfunction PLoS One 2009 4 7 e6197 19593388 PMC2703798
  109. [147]Kiyota T Yamamoto M Schroder B Jacobsen MT Swan RJ Lambert MP Klein WL Gendelman HE Ransohoff RM Ikezu T AAV1/2-mediated CNS gene delivery of dominant-negative CCL2 mutant suppresses gliosis, beta-amyloidosis, and learning impairment of APP/PS1 mice Mol Ther 2009 17 5 803 809 19277012 PMC2709991
  110. [148]Bulloch K Miller MM Gal-Toth J Milner TA Gottfried-Blackmore A Waters EM Kaunzner UW Liu K Lindquist R Nussenzweig MC Steinman RM McEwen BS CD11c/EYFP transgene illuminates a discrete network of dendritic cells within the embryonic, neonatal, adult, and injured mouse brain J Comp Neurol 2008 508 5 687 710 18386786
  111. [149]Hume DA Macrophages as APC and the dendritic cell myth J Immunol 2008 181 9 5829 5835 18941170
  112. [150]Butovsky O Kunis G Koronyo-Hamaoui M Schwartz M Selective ablation of bone marrow-derived dendritic cells increases amyloid plaques in a mouse Alzheimer’s disease model Eur J Neurosci 2007 26 2 413 416 17623022
  113. [151]Town T Laouar Y Pittenger C Mori T Szekely CA Tan J Duman RS Flavell RA Blocking TGF-beta-Smad2/3 innate immune signaling mitigates Alzheimer-like pathology Nat Med 2008 14 6 681 687 18516051 PMC2649699
  114. [152]Geissmann F Jung S Littman DR Blood monocytes consist of two principal subsets with distinct migratory properties Immunity 2003 19 1 71 82 12871640

Cited by

Sorted by citations

Authors
Mandrekar-Colucci, S., & Landreth, G. E.
Affiliations
  • Case Western Reserve University (US)
  • Case Comprehensive Cancer Center (US)
ORCID
Landreth, Gary E.
Venue
CNS & Neurological Disorders - Drug Targets
Publisher
Bentham Science Publishers Ltd.
Published
2010-04-01
Volume
9
Issue
2
Pages
156-167
ISSN
  • 1568-007X (ISSN-L)
  • 1871-5273
DOI
10.2174/187152710791012071
PMC
PMC3653290
OpenAlex
W2024816116
Cited by
421
References
40
Citations by year
2026: 4 · 2025: 21 · 2024: 27 · 2023: 33 · 2022: 37 · 2021: 45 · 2020: 39 · 2019: 27 · 2018: 35 · 2017: 34 · 2016: 22 · 2015: 19 · 2014: 19 · 2013: 18 · 2012: 16
FWCI
11.05
Type
journal article
Language
en
Open access
Locations
  • CNS & Neurological Disorders - Drug Targets (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute on Aging (R01AG030482, R01AG016740, AG-16740)
  • National Institute of Neurological Disorders and Stroke (F31NS061445)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
Keywords
microglia, Alzheimer's disease, neuroinflammation, amyloid-beta, microglial activation, neuroprotection, phagocytosis, reactive oxygen and nitrogen species, chemokines, peripheral macrophages, monocyte infiltration, tissue repair
MeSH terms
Alzheimer Disease, Animals, Brain, Encephalitis, Gliosis, Humans, Cytokines, Amyloid beta-Peptides, Microglia, Inflammation Mediators

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review