CoChat
Sign Up
Cited by 679Neuroinflammation and Neurodegeneration MechanismsMultiple Sclerosis Research StudiesNeurological Disease Mechanisms and Treatments

Immune activation in brain aging and neurodegeneration: too much or too little?

Open access
Lucin, Kurt M., Wyss-Coray, Tony·2009·Neuron
DOI 10.1016/j.neuron.2009.08.039PMC PMC2834890
Open this paper in CoChat — free account

Abstract

Until recently, the brain was studied almost exclusively by neuroscientists and the immune system by immunologists, fuelling the notion that these systems represented two isolated entities. However, as more data suggest an important role of the immune system in regulating the progression of brain aging and neurodegenerative disease, it has become clear that the crosstalk between these systems can no longer be ignored and a new interdisciplinary approach is necessary. A central question that emerges is whether immune and inflammatory pathways become hyperactivated with age and promote degeneration or whether insufficient immune responses, which fail to cope with age-related stress, may contribute to disease. We try to explore here the consequences of gain versus loss of function with an emphasis on microglia as sensors and effectors of immune function in the brain, and we discuss the potential role of the peripheral environment in neurodegenerative diseases.

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 · 10.1016/j.neuron.2009.08.039

Cites

29 of 29 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: 136

  1. 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 1538 1543 18026097
  2. Akiyama H Barger S Barnum S Bradt B Bauer J Cole GM Cooper NR Eikelenboom P Emmerling M Fiebich BL Inflammation and Alzheimer’s disease. Neuroinflammation Working Group Neurobiol. Aging 2000 21 383 421 10858586 PMC3887148
  3. Aldskogius H Liu L Svensson M Glial responses to synaptic damage and plasticity J. Neurosci. Res 1999 58 33 41 10491570
  4. Amatniek JC Hauser WA DelCastillo-Castaneda C Jacobs DM Marder K Bell K Albert M Brandt J Stern Y Incidence and predictors of seizures in patients with Alzheimer's disease Epilepsia 2006 47 867 872 16686651
  5. Arancio O Zhang HP Chen X Lin C Trinchese F Puzzo D Liu S Hegde A Yan SF Stern A RAGE potentiates Abeta-induced perturbation of neuronal function in transgenic mice Embo J 2004 23 4096 4105 15457210 PMC524347
  6. Bales KR Verina T Cummins DJ Du Y Dodel RC Saura J Fishman CE DeLong CA Piccardo P Petegnief V Apolipoprotein E is essential for amyloid deposition in the APP(V717F) transgenic mouse model of Alzheimer's disease Proc Natl Acad Sci U S A 1999 96 15233 15238 10611368 PMC24803
  7. Banerjee R Mosley RL Reynolds AD Dhar A Jackson-Lewis V Gordon PH Przedborski S Gendelman HE Adaptive immune neuroprotection in G93A-SOD1 amyotrophic lateral sclerosis mice PLoS ONE 2008 3 e2740 18648532 PMC2481277
  8. Beers DR Henkel JS Zhao W Wang J Appel SH CD4+ T cells support glial neuroprotection, slow disease progression, and modify glial morphology in an animal model of inherited ALS Proc Natl Acad Sci U S A 2008 105 15558 15563 18809917 PMC2547419
  9. Berchtold NC Cribbs DH Coleman PD Rogers J Head E Kim R Beach T Miller C Troncoso J Trojanowski JQ Gene expression changes in the course of normal brain aging are sexually dimorphic Proc Natl Acad Sci U S A 2008 105 15605 15610 18832152 PMC2563070
  10. Betmouni S Perry VH Gordon JL Evidence for an early inflammatory response in the central nervous system of mice with scrapie Neuroscience 1996 74 1 5 8843071
  11. Bjorkqvist M Wild EJ Thiele J Silvestroni A Andre R Lahiri N Raibon E Lee RV Benn CL Soulet D A novel pathogenic pathway of immune activation detectable before clinical onset in Huntington's disease J Exp Med 2008 205 1869 1877 18625748 PMC2525598
  12. Blattler T Brandner S Raeber AJ Klein MA Voigtlander T Weissmann C Aguzzi A PrP-expressing tissue required for transfer of scrapie infectivity from spleen to brain Nature 1997 389 69 73 9288968
  13. Boulanger LM Immune proteins in brain development and synaptic plasticity Neuron 2009 this issue. 19840552
  14. Bradl M Bauer J Flugel A Wekerle H Lassmann H Complementary contribution of CD4 and CD8 T lymphocytes to T-cell infiltration of the intact and the degenerative spinal cord Am J Pathol 2005 166 1441 1450 15855644 PMC1606398
  15. Brochard V Combadiere B Prigent A Laouar Y Perrin A Beray-Berthat V Bonduelle O Alvarez-Fischer D Callebert J Launay JM Infiltration of CD4+ lymphocytes into the brain contributes to neurodegeneration in a mouse model of Parkinson disease J Clin Invest 2009 119 182 192 19104149 PMC2613467
  16. Bulloch K Miller MM Gal-Toth J Milner TA Gottfried-Blackmore A Waters EM Kaunzner UW Liu K Lindquist R Nussenzweig MC CD11c/EYFP transgene illuminates a discrete network of dendritic cells within the embryonic, neonatal, adult, and injured mouse brain J Comp Neurol 2008 508 687 710 18386786
  17. Carpentier P Palmer T Immune influence on neural stem cell regulation and function Neuron 2009 this issue. PMC2789107 19840551
  18. Caso JR Pradillo JM Hurtado O Lorenzo P Moro MA Lizasoain I Toll-like receptor 4 is involved in brain damage and inflammation after experimental stroke Circulation 2007 115 1599 1608 17372179
  19. Chapman MR Robinson LS Pinkner JS Roth R Heuser J Hammar M Normark S Hultgren SJ Role of Escherichia coli curli operons in directing amyloid fiber formation Science 2002 295 851 855 11823641 PMC2838482
  20. Chen H Jacobs E Schwarzschild MA McCullough ML Calle EE Thun MJ Ascherio A Nonsteroidal antiinflammatory drug use and the risk for Parkinson's disease Ann Neurol 2005 58 963 967 16240369
  21. Chiu IM Chen A Zheng Y Kosaras B Tsiftsoglou SA Vartanian TK Brown RH Jr Carroll MC T lymphocytes potentiate endogenous neuroprotective inflammation in a mouse model of ALS Proc Natl Acad Sci U S A 2008 105 17913 17918 18997009 PMC2581614
  22. 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 32301 32308 10542270
  23. 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 Neuroinflammation 2006 3 27 17005052 PMC1609108
  24. Cunningham C Wilcockson DC Campion S Lunnon K Perry VH Central and systemic endotoxin challenges exacerbate the local inflammatory response and increase neuronal death during chronic neurodegeneration J Neurosci 2005 25 9275 9284 16207887 PMC6725757
  25. 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 2089 2102 19228962 PMC6666330
  26. Dandoy-Dron F Guillo F Benboudjema L Deslys J-P Lasmézas C Dormont D Tovey MG Dron M Gene expression in scrapie. Cloning of a new scrapie–responsive gene and the identification of increased levels of seven other mRNA transcipts J. Biol. Chem 1998 273 7691 7697 9516475
  27. Delgado MA Elmaoued RA Davis AS Kyei G Deretic V Toll-like receptors control autophagy EMBO J 2008 27 1110 1121 18337753 PMC2323261
  28. 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 13 432 438 17351623
  29. Fabene PF Navarro MG Martinello M Rossi B Merigo F Ottoboni L Bach S Angiari S Benati D Chakir A A role for leukocyte-endothelial adhesion mechanisms in epilepsy Nat Med 2008 14 1377 1383 19029985 PMC2710311
  30. Fan R Xu F Previti ML Davis J Grande AM Robinson JK Van Nostrand WE Minocycline reduces microglial activation and improves behavioral deficits in a transgenic model of cerebral microvascular amyloid J Neurosci 2007 27 3057 3063 17376966 PMC6672462
  31. Fassbender K Walter S Kuhl S Landmann R Ishii K Bertsch T Stalder AK Muehlhauser F Liu Y Ulmer AJ The LPS receptor (CD14) links innate immunity with Alzheimer's disease FASEB J 2004 18 203 205 14597556
  32. Fiala M Liu PT Espinosa-Jeffrey A Rosenthal MJ Bernard G Ringman JM Sayre J Zhang L Zaghi J Dejbakhsh S 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 2007 104 12849 12854 17652175 PMC1937555
  33. 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 84 225 233 1414275
  34. Frank-Cannon TC Tran T Ruhn KA Martinez TN Hong J Marvin M Hartley M Trevino I O'Brien DE Casey B Parkin deficiency increases vulnerability to inflammation-related nigral degeneration J Neurosci 2008 28 10825 10834 18945890 PMC2603252
  35. Fraser H Brown KL Stewart K McConnell I McBride P Williams A Replication of scrapie in spleens of SCID mice follows reconstitution with wild-type mouse bone marrow J Gen Virol 1996 77 Pt 8 1935 1940 8760445
  36. Gasque P Dean YD McGreal EP Beek JV Morgan BP Complement components of the innate immune system in health and disease in the CNS Immunopharmacology 2000 49 171 186 10904116
  37. Godoy MC Tarelli R Ferrari CC Sarchi MI Pitossi FJ Central and systemic IL-1 exacerbates neurodegeneration and motor symptoms in a model of Parkinson's disease Brain 2008 131 1880 1894 18504291 PMC2442423
  38. Gowing G Philips T Van Wijmeersch B Audet JN Dewil M Van Den Bosch L Billiau AD Robberecht W Julien JP Ablation of proliferating microglia does not affect motor neuron degeneration in amyotrophic lateral sclerosis caused by mutant superoxide dismutase J Neurosci 2008 28 10234 10244 18842883 PMC6671032
  39. Gutierrez MG Master SS Singh SB Taylor GA Colombo MI Deretic V Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages Cell 2004 119 753 766 15607973
  40. Hammer ND Schmidt JC Chapman MR The curli nucleator protein, CsgB, contains an amyloidogenic domain that directs CsgA polymerization Proc Natl Acad Sci U S A 2007 104 12494 12499 17636121 PMC1941497
  41. Hanisch UK Microglia as a source and target of cytokines Glia 2002 40 140 155 12379902
  42. Hanisch UK Kettenmann H Microglia: active sensor and versatile effector cells in the normal and pathologic brain Nat Neurosci 2007 10 1387 1394 17965659
  43. Herber DL Roth LM Wilson D Wilson N Mason JE Morgan D Gordon MN Time-dependent reduction in Abeta levels after intracranial LPS administration in APP transgenic mice Exp Neurol 2004 190 245 253 15473997
  44. Hoek RM Ruuls SR Murphy CA Wright GJ Goddard R Zurawski SM Blom B Homola ME Streit WJ Brown MH Down-regulation of the macrophage lineage through interaction with OX2 (CD200) Science 2000 290 1768 1771 11099416
  45. Holers VM Rich RR Complement Clinical Immunology Principles and Practice 1996 St. Louis, Missouri Mosby–Year Book 363 391
  46. Holmes C El-Okl M Williams AL Cunningham C Wilcockson D Perry VH Systemic infection, interleukin 1beta, and cognitive decline in Alzheimer's disease J Neurol Neurosurg Psychiatry 2003 74 788 789 12754353 PMC1738504
  47. Hsieh CL Koike M Spusta S Niemi E Yenari M Nakamura MC Seaman WE A Role for TREM2 Ligands in the Phagocytosis of Apoptotic Neuronal Cells by Microglia J Neurochem 2009 PMC3087597 19302484
  48. Iwasaki A Medzhitov R Toll-like receptor control of the adaptive immune responses Nat Immunol 2004 5 987 995 15454922
  49. Jaeger PA Wyss-Coray T All-you-can-eat: autophagy in neurodegeneration and neuroprotection Mol Neurodegener 2009 4 16 19348680 PMC2679749
  50. Jin JJ Kim HD Maxwell JA Li L Fukuchi K Toll-like receptor 4-dependent upregulation of cytokines in a transgenic mouse model of Alzheimer's disease J Neuroinflammation 2008 5 23 18510752 PMC2430555
  51. Kalman J Kitajka K Pakaski M Zvara A Juhasz A Vincze G Janka Z Puskas LG Gene expression profile analysis of lymphocytes from Alzheimer's patients Psychiatr Genet 2005 15 1 6 15722950
  52. Kang J Rivest S MyD88-deficient bone marrow cells accelerate onset and reduce survival in a mouse model of amyotrophic lateral sclerosis J Cell Biol 2007 179 1219 1230 18086918 PMC2140021
  53. Kerfoot SM D'Mello C Nguyen H Ajuebor MN Kubes P Le T Swain MG TNF-alpha-secreting monocytes are recruited into the brain of cholestatic mice Hepatology 2006 43 154 162 16374849
  54. Klionsky DJ Emr SD Autophagy as a regulated pathway of cellular degradation Science 2000 290 1717 1721 11099404 PMC2732363
  55. Kokovay E Cunningham LA Bone marrow-derived microglia contribute to the neuroinflammatory response and express iNOS in the MPTP mouse model of Parkinson's disease Neurobiol Dis 2005 19 471 478 16023589
  56. Koning N Bo L Hoek RM Huitinga I Downregulation of macrophage inhibitory molecules in multiple sclerosis lesions Ann Neurol 2007 62 504 514 17879969
  57. Kurkowska-Jastrzebska I Wronska A Kohutnicka M Czlonkowski A Czlonkowska A The inflammatory reaction following 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine intoxication in mouse Exp Neurol 1999 156 50 61 10192776
  58. Leadbetter EA Rifkin IR Hohlbaum AM Beaudette BC Shlomchik MJ Marshak-Rothstein A Chromatin-IgG complexes activate B cells by dual engagement of IgM and Toll-like receptors Nature 2002 416 603 607 11948342
  59. Lee C-K Weindruch R Prolla TA Gene-expression profile of the ageing brain in mice Nat. Genet 2000 25 294 297 10888876
  60. Lehnardt S Massillon L Follett P Jensen FE Ratan R Rosenberg PA Volpe JJ Vartanian T Activation of innate immunity in the CNS triggers neurodegeneration through a Toll-like receptor 4-dependent pathway Proc Natl Acad Sci U S A 2003 100 8514 8519 12824464 PMC166260
  61. Lehnardt S Schott E Trimbuch T Laubisch D Krueger C Wulczyn G Nitsch R Weber JR A vicious cycle involving release of heat shock protein 60 from injured cells and activation of toll-like receptor 4 mediates neurodegeneration in the CNS J Neurosci 2008 28 2320 2331 18322079 PMC6671170
  62. Letiembre M Hao W Liu Y Walter S Mihaljevic I Rivest S Hartmann T Fassbender K Innate immune receptor expression in normal brain aging Neuroscience 2007 146 248 254 17293054
  63. Levites Y Das P Price RW Rochette MJ Kostura LA McGowan EM Murphy MP Golde TE Anti-Abeta42- and anti-Abeta40-specific mAbs attenuate amyloid deposition in an Alzheimer disease mouse model J Clin Invest 2006 116 193 201 16341263 PMC1307561
  64. 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 1778 1789 15857927
  65. Lu T Pan Y Kao SY Li C Kohane I Chan J Yankner BA Gene regulation and DNA damage in the ageing human brain Nature 2004 429 883 891 15190254
  66. Maes OC Xu S Yu B Chertkow HM Wang E Schipper HM Transcriptional profiling of Alzheimer blood mononuclear cells by microarray Neurobiol Aging 2007 28 1795 1809 16979800
  67. 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 6333 6341 18562603 PMC3329761
  68. Majed HH Chandran S Niclou SP Nicholas RS Wilkins A Wing MG Rhodes KE Spillantini MG Compston A A novel role for Sema3A in neuroprotection from injury mediated by activated microglia J Neurosci 2006 26 1730 1738 16467521 PMC6793642
  69. Majumdar A Chung H Dolios G Wang R Asamoah N Lobel P Maxfield FR Degradation of fibrillar forms of Alzheimer's amyloid beta-peptide by macrophages Neurobiol Aging 2008 29 707 715 17222479 PMC2424018
  70. Majumdar A Cruz D Asamoah N Buxbaum A Sohar I Lobel P Maxfield FR Activation of microglia acidifies lysosomes and leads to degradation of Alzheimer amyloid fibrils Mol Biol Cell 2007 18 1490 1496 17314396 PMC1838985
  71. 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 18 134 142 15649704
  72. 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 4252 4262 19339619 PMC3034143
  73. McCoy MK Martinez TN Ruhn KA Szymkowski DE Smith CG Botterman BR Tansey KE Tansey MG Blocking soluble tumor necrosis factor signaling with dominant-negative tumor necrosis factor inhibitor attenuates loss of dopaminergic neurons in models of Parkinson's disease J Neurosci 2006 26 9365 9375 16971520 PMC3707118
  74. McGeer PL Itagaki S Akiyama H McGeer EG Rate of cell death in parkinsonism indicates active neuropathological process Ann Neurol 1988 24 574 576 3239957
  75. 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 47 425 432 8757015
  76. Medawar PB Immunity to homologous grafted skin; the fate of skin homografts transplanted to the brain, to subcutaneous tissue, and to the anterior chamber of the eye Br J Exp Pathol 1948 29 58 69 18865105 PMC2073079
  77. Monsonego A Imitola J Petrovic S Zota V Nemirovsky A Baron R Fisher Y Owens T Weiner HL Abeta-induced meningoencephalitis is IFN-{gamma}-dependent and is associated with T cell-dependent clearance of Abeta in a mouse model of Alzheimer's disease Proc Natl Acad Sci U S A 2006 103 5048 5053 16549802 PMC1458792
  78. 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 46 369 379 15095367
  79. Mount MP Lira A Grimes D Smith PD Faucher S Slack R Anisman H Hayley S Park DS Involvement of interferon-gamma in microglial-mediated loss of dopaminergic neurons J Neurosci 2007 27 3328 3337 17376993 PMC6672486
  80. Neumann H Boucraut J Hahnel C Misgeld T Wekerle H Neuronal control of MHC class II inducibility in rat astrocytes and microglia Eur J Neurosci 1996 8 2582 2590 8996807
  81. Nguyen MD D'Aigle T Gowing G Julien JP Rivest S Exacerbation of motor neuron disease by chronic stimulation of innate immunity in a mouse model of amyotrophic lateral sclerosis J Neurosci 2004 24 1340 1349 14960605 PMC6730331
  82. Nguyen MD Julien JP Rivest S Innate immunity: The missing link in neuroprotection and neurodegeneration? Nat. Rev. Neurosci 2002 3 216 227 11994753
  83. Nixon RA Wegiel J Kumar A Yu WH Peterhoff C Cataldo A Cuervo AM Extensive involvement of autophagy in Alzheimer disease: an immuno-electron microscopy study J Neuropathol Exp Neurol 2005 64 113 122 15751225
  84. Ohashi K Burkart V Flohe S Kolb H Cutting edge: heat shock protein 60 is a putative endogenous ligand of the toll-like receptor-4 complex J Immunol 2000 164 558 561 10623794
  85. Oldenborg PA Gresham HD Lindberg FP CD47-signal regulatory protein alpha (SIRPalpha) regulates Fcgamma and complement receptor-mediated phagocytosis J Exp Med 2001 193 855 862 11283158 PMC2193364
  86. Orr HT Zoghbi HY Reversing neurodegeneration: A promise unfolds Cell 2000 101 1 4 10778849
  87. Palin K Cunningham C Forse P Perry VH Platt N Systemic inflammation switches the inflammatory cytokine profile in CNS Wallerian degeneration Neurobiol Dis 2008 30 19 29 18255301
  88. Palm NW Medzhitov R Pattern recognition receptors and control of adaptive immunity Immunol Rev 2009 227 221 233 19120487
  89. Palop JJ Chin J Roberson ED Wang J Thwin MT Bien-Ly N Yoo J Ho KO Yu GQ Kreitzer A Aberrant excitatory neuronal activity and compensatory remodeling of inhibitory hippocampal circuits in mouse models of Alzheimer's disease Neuron 2007 55 697 711 17785178 PMC8055171
  90. Paresce DM Chung H Maxfield FR Slow degradation of aggregates of the Alzheimer's disease amyloid beta-protein by microglial cells J Biol Chem 1997 272 29390 29397 9361021
  91. Perry VH Cunningham C Holmes C Systemic infections and inflammation affect chronic neurodegeneration Nat Rev Immunol 2007 7 161 167 17220915
  92. Pickford F Masliah E Britschgi M Lucin K Narasimhan R Jaeger PA Small S Spencer B Rockenstein E Levine B Wyss-Coray T The autophagy-related protein beclin 1 shows reduced expression in early Alzheimer disease and regulates amyloid beta accumulation in mice J Clin Invest 2008 118 2190 2199 18497889 PMC2391284
  93. Pocock JM Kettenmann H Neurotransmitter receptors on microglia Trends Neurosci 2007 30 527 535 17904651
  94. Ponomarev ED Shriver LP Maresz K Dittel BN Microglial cell activation and proliferation precedes the onset of CNS autoimmunity J Neurosci Res 2005 81 374 389 15959904
  95. Popovich PG Guan Z McGaughy V Fisher L Hickey WF Basso DM The neuropathological and behavioral consequences of intraspinal microglial/macrophage activation J Neuropathol Exp Neurol 2002 61 623 633 12125741
  96. Priller J Prinz M Heikenwalder M Zeller N Schwarz P Heppner FL Aguzzi A Early and rapid engraftment of bone marrow-derived microglia in scrapie J Neurosci 2006 26 11753 11762 17093096 PMC6674798
  97. Ray S Britschgi M Herbert C Takeda-Uchimura Y Boxer A Blennow K Friedman LF Galasko DR Jutel M Karydas A Classification and prediction of clinical Alzheimer's diagnosis based on plasma signaling proteins Nat Med 2007 13 1369–1362. 17934472
  98. Reale M Iarlori C Gambi F Lucci I Salvatore M Gambi D Acetylcholinesterase inhibitors effects on oncostatin-M, interleukin-1 beta and interleukin-6 release from lymphocytes of Alzheimer's disease patients Exp Gerontol 2005 40 165 171 15763393
  99. 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 5784 5793 18509040 PMC6670789
  100. Rodriguez M Alvarez-Erviti L Blesa FJ Rodriguez-Oroz MC Arina A Melero I Ramos LI Obeso JA Bone-marrow-derived cell differentiation into microglia: a study in a progressive mouse model of Parkinson's disease Neurobiol Dis 2007 28 316 325 17897835
  101. 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 1988 9 339 349 3263583
  102. Sanjuan MA Dillon CP Tait SW Moshiach S Dorsey F Connell S Komatsu M Tanaka K Cleveland JL Withoff S Green DR Toll-like receptor signalling in macrophages links the autophagy pathway to phagocytosis Nature 2007 450 1253 1257 18097414
  103. Savill J Dransfield I Gregory C Haslett C A blast from the past: clearance of apoptotic cells regulates immune responses Nat Rev Immunol 2002 2 965 975 12461569
  104. Scherzer CR Eklund AC Morse LJ Liao Z Locascio JJ Fefer D Schwarzschild MA Schlossmacher MG Hauser MA Vance JM Molecular markers of early Parkinson's disease based on gene expression in blood Proc Natl Acad Sci U S A 2007 104 955 960 17215369 PMC1766335
  105. Sedgwick JD Schwender S Imrich H Dorries R Butcher GW ter Meulen V Isolation and direct characterization of resident microglial cells from the normal and inflamed central nervous system Proc Natl Acad Sci U S A 1991 88 7438 7442 1651506 PMC52311
  106. Seong SY Matzinger P Hydrophobicity: an ancient damage-associated molecular pattern that initiates innate immune responses Nat Rev Immunol 2004 4 469 478 15173835
  107. Sherman MY Goldberg AL Cellular defenses against unfolded proteins: A cell biologist thinks about neurodegenerative disease Neuron 2001 29 15 32 11182078
  108. Shui W Sheu L Liu J Smart B Petzold CJ Hsieh TY Pitcher A Keasling JD Bertozzi CR Membrane proteomics of phagosomes suggests a connection to autophagy Proc Natl Acad Sci U S A 2008 105 16952 16957 18971338 PMC2579359
  109. 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 49 489 502 16476660
  110. Singhrao SK Increased complement biosynthesis by microglia and complement activation on neurons in Huntington’s disease Exp. Neurol 1999 159 362 376 10506508
  111. Smiley ST King JA Hancock WW Fibrinogen stimulates macrophage chemokine secretion through toll-like receptor 4 J Immunol 2001 167 2887 2894 11509636
  112. Smith RE Patel V Seatter SD Deehan MR Brown MH Brooke GP Goodridge HS Howard CJ Rigley KP Harnett W Harnett MM A novel MyD-1 (SIRP-1alpha) signaling pathway that inhibits LPS-induced TNFalpha production by monocytes Blood 2003 102 2532 2540 12805067
  113. Song W-C Sarrias MR Lambris JD Complement and innate immunity Immunopharmacology 2000 49 187 198 10904117
  114. Sriram K Matheson JM Benkovic SA Miller DB Luster MI O'Callaghan JP Mice deficient in TNF receptors are protected against dopaminergic neurotoxicity: implications for Parkinson's disease Faseb J 2002 16 1474 1476 12205053
  115. 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 11125 11132 16319312 PMC6725647
  116. Stevens B Allen NJ Vazquez LE Howell GR Christopherson KS Nouri N Micheva KD Mehalow AK Huberman AD Stafford B The classical complement cascade mediates CNS synapse elimination Cell 2007 131 1164 1178 18083105
  117. Streit WJ Miller KR Lopes KO Njie E Microglial degeneration in the aging brain--bad news for neurons? Front Biosci 2008 13 3423 3438 18508444
  118. Szabo P Relkin N Weksler ME Natural human antibodies to amyloid beta peptide Autoimmun Rev 2008 7 415 420 18558354
  119. 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 3006 3019 16984903 PMC2445613
  120. Tang SC Arumugam TV Xu X Cheng A Mughal MR Jo DG Lathia JD Siler DA Chigurupati S Ouyang X Pivotal role for neuronal Toll-like receptors in ischemic brain injury and functional deficits Proc Natl Acad Sci U S A 2007 104 13798 13803 17693552 PMC1959462
  121. Tenner AJ Membrane receptors for soluble defense collagens Curr. Opin. Immunol 1999 11 34 41 10047541
  122. 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 2002 124 83 92 11958825
  123. 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 14 681 687 18516051 PMC2649699
  124. Viglianti GA Lau CM Hanley TM Miko BA Shlomchik MJ Marshak-Rothstein A Activation of autoreactive B cells by CpG dsDNA Immunity 2003 19 837 847 14670301
  125. Vlad SC Miller DR Kowall NW Felson DT Protective effects of NSAIDs on the development of Alzheimer disease Neurology 2008 70 1672 1677 18458226 PMC2758242
  126. Walker LC LeVine H The cerebral proteopathies - Neurodegenerative disorders of protein conformation and assembly Mol. Neurobiol 2000 21 83 95 11327151
  127. 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 20 947 956 17982277
  128. Wang CW Klionsky DJ The molecular mechanism of autophagy Mol Med 2003 9 65 76 12865942 PMC1430730
  129. Webb JL Ravikumar B Atkins J Skepper JN Rubinsztein DC Alpha-Synuclein is degraded by both autophagy and the proteasome J Biol Chem 2003 278 25009 25013 12719433
  130. Webster S Lue L-F Brachova L Tenner AJ McGeer PL Terai K Walker DG Bradt B Cooper NR Rogers J Molecular and cellular characterization of the membrane attack complex, C5b-9, in Alzheimer’s disease Neurobiol. Aging 1997 18 415 421 9330973
  131. Wegiel J Wisniewski HM The complex of microglial cells and amyloid star in three-dimensional reconstruction Acta Neuropathol 1990 81 116 120 2082651
  132. Williams AE Ryder S Blakemore WF Monocyte recruitment into the scrapie-affected brain Acta Neuropathol 1995 90 164 169 7484092
  133. Wyss-Coray T Lin C Yan F Yu G Rohde M McConlogue L Masliah E Mucke L TGF-β1 promotes microglial amyloid-β clearance and reduces plaque burden in transgenic mice Nat. Med 2001 7 612 618 11329064
  134. 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 10837 10842 12119423 PMC125059
  135. Xu Y Jagannath C Liu XD Sharafkhaneh A Kolodziejska KE Eissa NT Toll-like receptor 4 is a sensor for autophagy associated with innate immunity Immunity 2007 27 135 144 17658277 PMC2680670
  136. Yamada T McGeer PL McGeer EG Lewy bodies in Parkinson’s disease are recognized by antibodies to complement proteins Acta Neuropathol 1992 84 100 104 1502878

Cited by

Sorted by citations

Authors
Lucin, K. M., & Wyss-Coray, T.
Affiliations
VA Palo Alto Health Care System (US)
Venue
Neuron
Publisher
Elsevier BV
Published
2009-10
Volume
64
Issue
1
Pages
110-122
ISSN
0896-6273 (ISSN-L)
DOI
10.1016/j.neuron.2009.08.039
PMC
PMC2834890
OpenAlex
W2085667648
Cited by
679
References
29
Citations by year
2026: 12 · 2025: 19 · 2024: 19 · 2023: 29 · 2022: 46 · 2021: 40 · 2020: 39 · 2019: 36 · 2018: 43 · 2017: 47 · 2016: 47 · 2015: 43 · 2014: 51 · 2013: 53 · 2012: 54
FWCI
4.06
Type
journal article
Language
en
Open access
Licence
Locations
  • Neuron (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute on Aging (R01AG027505, AG30144, R01AG030144, AG27505)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
Keywords
brain aging, neurodegeneration, neuroinflammation, microglia, immune activation, neuroimmune interactions, gain and loss of function, age-related immune dysfunction
MeSH terms
Aging, Animals, Brain, Humans, Models, Neurological, Neurons, Neuroimmunomodulation, Microglia, Neurodegenerative Diseases

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