Microglia are resident cells of the brain that regulate brain development, maintenance of neuronal networks, and injury repair. Microglia serve as brain macrophages but are distinct from other tissue macrophages owing to their unique homeostatic phenotype and tight regulation by the central nervous system (CNS) microenvironment. They are responsible for the elimination of microbes, dead cells, redundant synapses, protein aggregates, and other particulate and soluble antigens that may endanger the CNS. Furthermore, as the primary source of proinflammatory cytokines, microglia are pivotal mediators of neuroinflammation and can induce or modulate a broad spectrum of cellular responses. Alterations in microglia functionality are implicated in brain development and aging, as well as in neurodegeneration. Recent observations about microglia ontogeny combined with extensive gene expression profiling and novel tools to study microglia biology have allowed us to characterize the spectrum of microglial phenotypes during development, homeostasis, and disease. In this article, we review recent advances in our understanding of the biology of microglia, their contribution to homeostasis, and their involvement in neurodegeneration. Moreover, we highlight the complexity of targeting microglia for therapeutic intervention in neurodegenerative diseases.


Article metrics loading...

Loading full text...

Full text loading...


Literature Cited

  1. Ginhoux F, Greter M, Leboeuf M, Nandi S, See P. 1.  et al. 2010. Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science 330:841–45 [Google Scholar]
  2. Schulz C, Gomez Perdiguero E, Chorro L, Szabo-Rogers H, Cagnard N. 2.  et al. 2012. A lineage of myeloid cells independent of Myb and hematopoietic stem cells. Science 336:86–90 [Google Scholar]
  3. Goldmann T, Wieghofer P, Jordao MJ, Prutek F, Hagemeyer N. 3.  et al. 2016. Origin, fate and dynamics of macrophages at central nervous system interfaces. Nat. Immunol. 17:797–805 [Google Scholar]
  4. Perdiguero EG, Geissmann F. 4.  2016. The development and maintenance of resident macrophages. Nat. Immunol. 17:2–8 [Google Scholar]
  5. Dai XM, Ryan GR, Hapel AJ, Dominguez MG, Russell RG. 5.  et al. 2002. Targeted disruption of the mouse colony-stimulating factor 1 receptor gene results in osteopetrosis, mononuclear phagocyte deficiency, increased primitive progenitor cell frequencies, and reproductive defects. Blood 99:111–20 [Google Scholar]
  6. Elmore MR, Najafi AR, Koike MA, Dagher NN, Spangenberg EE. 6.  et al. 2014. Colony-stimulating factor 1 receptor signaling is necessary for microglia viability, unmasking a microglia progenitor cell in the adult brain. Neuron 82:380–97 [Google Scholar]
  7. Wang Y, Szretter KJ, Vermi W, Gilfillan S, Rossini C. 7.  et al. 2012. IL-34 is a tissue-restricted ligand of CSF1R required for the development of Langerhans cells and microglia. Nat. Immunol. 13:753–60 [Google Scholar]
  8. Greter M, Lelios I, Pelczar P, Hoeffel G, Price J. 8.  et al. 2012. Stroma-derived interleukin-34 controls the development and maintenance of Langerhans cells and the maintenance of microglia. Immunity 37:1050–60 [Google Scholar]
  9. Chitu V, Gokhan S, Nandi S, Mehler MF, Stanley ER. 9.  2016. Emerging roles for CSF-1 receptor and its ligands in the nervous system. Trends Neurosci 39:378–93 [Google Scholar]
  10. Lin H, Lee E, Hestir K, Leo C, Huang M. 10.  et al. 2008. Discovery of a cytokine and its receptor by functional screening of the extracellular proteome. Science 320:807–11 [Google Scholar]
  11. Ma X, Lin WY, Chen Y, Stawicki S, Mukhyala K. 11.  et al. 2012. Structural basis for the dual recognition of helical cytokines IL-34 and CSF-1 by CSF-1R. Structure 20:676–87 [Google Scholar]
  12. Nimmerjahn A, Kirchhoff F, Helmchen F. 12.  2005. Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 308:1314–18 [Google Scholar]
  13. Davalos D, Grutzendler J, Yang G, Kim JV, Zuo Y. 13.  et al. 2005. ATP mediates rapid microglial response to local brain injury in vivo. Nat. Neurosci. 8:752–58 [Google Scholar]
  14. Wake H, Moorhouse AJ, Jinno S, Kohsaka S, Nabekura J. 14.  2009. Resting microglia directly monitor the functional state of synapses in vivo and determine the fate of ischemic terminals. J. Neurosci. 29:3974–80 [Google Scholar]
  15. Tam WY, Ma CH. 15.  2014. Bipolar/rod-shaped microglia are proliferating microglia with distinct M1/M2 phenotypes. Sci. Rep. 4:7279 [Google Scholar]
  16. Saijo K, Crotti A, Glass CK. 16.  2013. Regulation of microglia activation and deactivation by nuclear receptors. Glia 61:104–11 [Google Scholar]
  17. Heneka MT, Golenbock DT, Latz E. 17.  2015. Innate immunity in Alzheimer's disease. Nat. Immunol. 16:229–36 [Google Scholar]
  18. Wu J, Chen ZJ. 18.  2014. Innate immune sensing and signaling of cytosolic nucleic acids. Annu. Rev. Immunol. 32:461–88 [Google Scholar]
  19. Sancho D, Reis e Sousa C. 19.  2012. Signaling by myeloid C-type lectin receptors in immunity and homeostasis. Annu. Rev. Immunol. 30:491–529 [Google Scholar]
  20. Areschoug T, Gordon S. 20.  2009. Scavenger receptors: role in innate immunity and microbial pathogenesis. Cell. Microbiol. 11:1160–69 [Google Scholar]
  21. Rebeck GW, LaDu MJ, Estus S, Bu G, Weeber EJ. 21.  2006. The generation and function of soluble apoE receptors in the CNS. Mol. Neurodegener. 1:15 [Google Scholar]
  22. Lemke G. 22.  2013. Biology of the TAM receptors. Cold Spring Harb. Perspect. Biol. 5:a009076 [Google Scholar]
  23. Fourgeaud L, Traves PG, Tufail Y, Leal-Bailey H, Lew ED. 23.  et al. 2016. TAM receptors regulate multiple features of microglial physiology. Nature 532:240–44 [Google Scholar]
  24. Mizutani M, Pino PA, Saederup N, Charo IF, Ransohoff RM. 24.  et al. 2012. The fractalkine receptor but not CCR2 is present on microglia from embryonic development throughout adulthood. J. Immunol. 188:29–36 [Google Scholar]
  25. Jung S, Aliberti J, Graemmel P, Sunshine MJ, Kreutzberg GW. 25.  et al. 2000. Analysis of fractalkine receptor CX3CR1 function by targeted deletion and green fluorescent protein reporter gene insertion. Mol. Cell. Biol. 20:4106–14 [Google Scholar]
  26. Colonna M, Wang Y. 26.  2016. TREM2 variants: new keys to decipher Alzheimer disease pathogenesis. Nat. Rev. Neurosci. 17:201–7 [Google Scholar]
  27. Linnartz-Gerlach B, Mathews M, Neumann H. 27.  2014. Sensing the neuronal glycocalyx by glial sialic acid binding immunoglobulin-like lectins. Neuroscience 275:113–24 [Google Scholar]
  28. Wright GJ, Cherwinski H, Foster-Cuevas M, Brooke G, Puklavec MJ. 28.  et al. 2003. Characterization of the CD200 receptor family in mice and humans and their interactions with CD200. J. Immunol. 171:3034–46 [Google Scholar]
  29. Zhang H, Li F, Yang Y, Chen J, Hu X. 29.  2015. SIRP/CD47 signaling in neurological disorders. Brain Res 1623:74–80 [Google Scholar]
  30. Goldmann T, Blank T, Prinz M. 30.  2016. Fine-tuning of type I IFN-signaling in microglia—implications for homeostasis, CNS autoimmunity and interferonopathies. Curr. Opin. Neurobiol. 36:38–42 [Google Scholar]
  31. Pocock JM, Kettenmann H. 31.  2007. Neurotransmitter receptors on microglia. Trends Neurosci 30:527–35 [Google Scholar]
  32. Taylor DL, Jones F, Kubota ES, Pocock JM. 32.  2005. Stimulation of microglial metabotropic glutamate receptor mGlu2 triggers tumor necrosis factor α-induced neurotoxicity in concert with microglial-derived Fas ligand. J. Neurosci. 25:2952–64 [Google Scholar]
  33. Hagino Y, Kariura Y, Manago Y, Amano T, Wang B. 33.  et al. 2004. Heterogeneity and potentiation of AMPA type of glutamate receptors in rat cultured microglia. Glia 47:68–77 [Google Scholar]
  34. Appel SH, Zhao W, Beers DR, Henkel JS. 34.  2011. The microglial-motoneuron dialogue in ALS. Acta Myol 30:4–8 [Google Scholar]
  35. Sica A, Mantovani A. 35.  2012. Macrophage plasticity and polarization: in vivo veritas. J. Clin. Investig. 122:787–95 [Google Scholar]
  36. Wes PD, Holtman IR, Boddeke EW, Moller T, Eggen BJ. 36.  2016. Next generation transcriptomics and genomics elucidate biological complexity of microglia in health and disease. Glia 64:197–213 [Google Scholar]
  37. Butovsky O, Jedrychowski MP, Moore CS, Cialic R, Lanser AJ. 37.  et al. 2014. Identification of a unique TGF-β-dependent molecular and functional signature in microglia. Nat. Neurosci. 17:131–43 [Google Scholar]
  38. Gosselin D, Link VM, Romanoski CE, Fonseca GJ, Eichenfield DZ. 38.  et al. 2014. Environment drives selection and function of enhancers controlling tissue-specific macrophage identities. Cell 159:1327–40 [Google Scholar]
  39. Zhang Y, Chen K, Sloan SA, Bennett ML, Scholze AR. 39.  et al. 2014. An RNA-sequencing transcriptome and splicing database of glia, neurons, and vascular cells of the cerebral cortex. J. Neurosci. 34:11929–47 [Google Scholar]
  40. Hickman SE, Kingery ND, Ohsumi TK, Borowsky ML, Wang LC. 40.  et al. 2013. The microglial sensome revealed by direct RNA sequencing. Nat. Neurosci. 16:1896–905 [Google Scholar]
  41. Ransohoff RM. 41.  2016. A polarizing question: Do M1 and M2 microglia exist?. Nat. Neurosci. 19:987–91 [Google Scholar]
  42. Chiu IM, Morimoto ET, Goodarzi H, Liao JT, O'Keeffe S. 42.  et al. 2013. A neurodegeneration-specific gene-expression signature of acutely isolated microglia from an amyotrophic lateral sclerosis mouse model. Cell Rep 4:385–401 [Google Scholar]
  43. Abutbul S, Shapiro J, Szaingurten-Solodkin I, Levy N, Carmy Y. 43.  et al. 2012. TGF-beta signaling through SMAD2/3 induces the quiescent microglial phenotype within the CNS environment. Glia 60:1160–71 [Google Scholar]
  44. Matcovitch-Natan O, Winter DR, Giladi A, Vargas Aguilar S, Spinrad A. 44.  et al. 2016. Microglia development follows a stepwise program to regulate brain homeostasis. Science 353:789–801 [Google Scholar]
  45. Grabert K, Michoel T, Karavolos MH, Clohisey S, Baillie JK. 45.  et al. 2016. Microglial brain region-dependent diversity and selective regional sensitivities to aging. Nat. Neurosci. 19:504–16 [Google Scholar]
  46. Hoban AE, Stilling RM, Ryan FJ, Shanahan F, Dinan TG. 46.  et al. 2016. Regulation of prefrontal cortex myelination by the microbiota. Transl. Psychiatry 6:e774 [Google Scholar]
  47. Ogbonnaya ES, Clarke G, Shanahan F, Dinan TG, Cryan JF, O'Leary OF. 47.  2015. Adult hippocampal neurogenesis is regulated by the microbiome. Biol. Psychiatry 78:e7–9 [Google Scholar]
  48. Mayer EA, Knight R, Mazmanian SK, Cryan JF, Tillisch K. 48.  2014. Gut microbes and the brain: paradigm shift in neuroscience. J. Neurosci. 34:15490–96 [Google Scholar]
  49. Marshall JK, Thabane M, Garg AX, Clark WF, Moayyedi P, Collins SM. 49.  2010. Eight year prognosis of postinfectious irritable bowel syndrome following waterborne bacterial dysentery. Gut 59:605–11 [Google Scholar]
  50. Yano JM, Yu K, Donaldson GP, Shastri GG, Ann P. 50.  et al. 2015. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell 161:264–76 [Google Scholar]
  51. Braniste V, Al-Asmakh M, Kowal C, Anuar F, Abbaspour A. 51.  et al. 2014. The gut microbiota influences blood-brain barrier permeability in mice. Sci. Transl. Med. 6:263ra158 [Google Scholar]
  52. Erny D, Hrabe de Angelis AL, Jaitin D, Wieghofer P, Staszewski O. 52.  et al. 2015. Host microbiota constantly control maturation and function of microglia in the CNS. Nat. Neurosci. 18:965–77 [Google Scholar]
  53. Villa A, Vegeto E, Poletti A, Maggi A. 53.  2016. Estrogens, neuroinflammation, and neurodegeneration. Endocr. Rev. 37:372–402 [Google Scholar]
  54. Schwarz JM, Bilbo SD. 54.  2012. Sex, glia, and development: interactions in health and disease. Horm. Behav. 62:243–53 [Google Scholar]
  55. Lenz KM, Nugent BM, McCarthy MM. 55.  2012. Sexual differentiation of the rodent brain: dogma and beyond. Front. Neurosci. 6:26 [Google Scholar]
  56. Tremblay ME, Zettel ML, Ison JR, Allen PD, Majewska AK. 56.  2012. Effects of aging and sensory loss on glial cells in mouse visual and auditory cortices. Glia 60:541–58 [Google Scholar]
  57. Poliani PL, Wang Y, Fontana E, Robinette ML, Yamanishi Y. 57.  et al. 2015. TREM2 sustains microglial expansion during aging and response to demyelination. J. Clin. Investig. 125:2161–70 [Google Scholar]
  58. Sierra A, Gottfried-Blackmore AC, McEwen BS, Bulloch K. 58.  2007. Microglia derived from aging mice exhibit an altered inflammatory profile. Glia 55:412–24 [Google Scholar]
  59. Hefendehl JK, Neher JJ, Suhs RB, Kohsaka S, Skodras A, Jucker M. 59.  2014. Homeostatic and injury-induced microglia behavior in the aging brain. Aging Cell 13:60–69 [Google Scholar]
  60. Safaiyan S, Kannaiyan N, Snaidero N, Brioschi S, Biber K. 60.  et al. 2016. Age-related myelin degradation burdens the clearance function of microglia during aging. Nat. Neurosci. 19:995–98 [Google Scholar]
  61. Squarzoni P, Thion MS, Garel S. 61.  2015. Neuronal and microglial regulators of cortical wiring: usual and novel guideposts. Front. Neurosci. 9:248 [Google Scholar]
  62. Arno B, Grassivaro F, Rossi C, Bergamaschi A, Castiglioni V. 62.  et al. 2014. Neural progenitor cells orchestrate microglia migration and positioning into the developing cortex. Nat. Commun. 5:5611 [Google Scholar]
  63. Li Y, Du XF, Du JL. 63.  2013. Resting microglia respond to and regulate neuronal activity in vivo. Commun. Integr. Biol. 6:e24493 [Google Scholar]
  64. Luo C, Koyama R, Ikegaya Y. 64.  2016. Microglia engulf viable newborn cells in the epileptic dentate gyrus. Glia 64:1508–17 [Google Scholar]
  65. Solano Fonseca R, Mahesula S, Apple DM, Raghunathan R, Dugan A. 65.  et al. 2016. Neurogenic niche microglia undergo positional remodeling and progressive activation contributing to age-associated reductions in neurogenesis. Stem Cells Dev 25:542–55 [Google Scholar]
  66. Kettenmann H, Kirchhoff F, Verkhratsky A. 66.  2013. Microglia: new roles for the synaptic stripper. Neuron 77:10–18 [Google Scholar]
  67. Tremblay ME, Stevens B, Sierra A, Wake H, Bessis A, Nimmerjahn A. 67.  2011. The role of microglia in the healthy brain. J. Neurosci. 31:16064–69 [Google Scholar]
  68. Schafer DP, Lehrman EK, Kautzman AG, Koyama R, Mardinly AR. 68.  et al. 2012. Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner. Neuron 74:691–705 [Google Scholar]
  69. Stevens B, Allen NJ, Vazquez LE, Howell GR, Christopherson KS. 69.  et al. 2007. The classical complement cascade mediates CNS synapse elimination. Cell 131:1164–78 [Google Scholar]
  70. Bialas AR, Stevens B. 70.  2013. TGF-beta signaling regulates neuronal C1q expression and developmental synaptic refinement. Nat. Neurosci. 16:1773–82 [Google Scholar]
  71. Paolicelli RC, Bolasco G, Pagani F, Maggi L, Scianni M. 71.  et al. 2011. Synaptic pruning by microglia is necessary for normal brain development. Science 333:1456–58 [Google Scholar]
  72. Hoshiko M, Arnoux I, Avignone E, Yamamoto N, Audinat E. 72.  2012. Deficiency of the microglial receptor CX3CR1 impairs postnatal functional development of thalamocortical synapses in the barrel cortex. J. Neurosci. 32:15106–11 [Google Scholar]
  73. Vezzani A, Viviani B. 73.  2015. Neuromodulatory properties of inflammatory cytokines and their impact on neuronal excitability. Neuropharmacology 96:70–82 [Google Scholar]
  74. Paulsen O, Sejnowski TJ. 74.  2000. Natural patterns of activity and long-term synaptic plasticity. Curr. Opin. Neurobiol. 10:172–79 [Google Scholar]
  75. Collingridge GL, Peineau S. 75.  2014. Strippers reveal their depressing secrets: removing AMPA receptors. Neuron 82:3–6 [Google Scholar]
  76. Zhang J, Malik A, Choi HB, Ko RW, Dissing-Olesen L, MacVicar BA. 76.  2014. Microglial CR3 activation triggers long-term synaptic depression in the hippocampus via NADPH oxidase. Neuron 82:195–207 [Google Scholar]
  77. Parkhurst CN, Yang G, Ninan I, Savas JN, 3rd Yates JR. 77.  et al. 2013. Microglia promote learning-dependent synapse formation through brain-derived neurotrophic factor. Cell 155:1596–609 [Google Scholar]
  78. Tong L, Prieto GA, Kramar EA, Smith ED, Cribbs DH. 78.  et al. 2012. Brain-derived neurotrophic factor-dependent synaptic plasticity is suppressed by interleukin-1β via p38 mitogen-activated protein kinase. J. Neurosci. 32:17714–24 [Google Scholar]
  79. Lynch MA. 79.  2015. Neuroinflammatory changes negatively impact on LTP: a focus on IL-1β.. Brain Res 1621:197–204 [Google Scholar]
  80. Coull JA, Beggs S, Boudreau D, Boivin D, Tsuda M. 80.  et al. 2005. BDNF from microglia causes the shift in neuronal anion gradient underlying neuropathic pain. Nature 438:1017–21 [Google Scholar]
  81. Stellwagen D, Malenka RC. 81.  2006. Synaptic scaling mediated by glial TNF-alpha. Nature 440:1054–59 [Google Scholar]
  82. Pascual O, Ben Achour S, Rostaing P, Triller A, Bessis A. 82.  2012. Microglia activation triggers astrocyte-mediated modulation of excitatory neurotransmission. PNAS 109:E197–205 [Google Scholar]
  83. Dissing-Olesen L, LeDue JM, Rungta RL, Hefendehl JK, Choi HB, MacVicar BA. 83.  2014. Activation of neuronal NMDA receptors triggers transient ATP-mediated microglial process outgrowth. J. Neurosci. 34:10511–27 [Google Scholar]
  84. Masuch A, Shieh CH, van Rooijen N, van Calker D, Biber K. 84.  2016. Mechanism of microglia neuroprotection: involvement of P2X7, TNFα, and valproic acid. Glia 64:76–89 [Google Scholar]
  85. Kato G, Inada H, Wake H, Akiyoshi R, Miyamoto A. 85.  et al. 2016. Microglial contact prevents excess depolarization and rescues neurons from excitotoxicity. eNeuro 3:e0004–16.2016 [Google Scholar]
  86. Barres BA. 86.  2008. The mystery and magic of glia: a perspective on their roles in health and disease. Neuron 60:430–40 [Google Scholar]
  87. Rothstein JD, Dykes-Hoberg M, Pardo CA, Bristol LA, Jin L. 87.  et al. 1996. Knockout of glutamate transporters reveals a major role for astroglial transport in excitotoxicity and clearance of glutamate. Neuron 16:675–86 [Google Scholar]
  88. Christian CA, Huguenard JR. 88.  2013. Astrocytes potentiate GABAergic transmission in the thalamic reticular nucleus via endozepine signaling. PNAS 110:20278–83 [Google Scholar]
  89. Lee M, Schwab C, McGeer PL. 89.  2011. Astrocytes are GABAergic cells that modulate microglial activity. Glia 59:152–65 [Google Scholar]
  90. Min KJ, Yang MS, Kim SU, Jou I, Joe EH. 90.  2006. Astrocytes induce hemeoxygenase-1 expression in microglia: a feasible mechanism for preventing excessive brain inflammation. J. Neurosci. 26:1880–87 [Google Scholar]
  91. Welser-Alves JV, Crocker SJ, Milner R. 91.  2011. A dual role for microglia in promoting tissue inhibitor of metalloproteinase (TIMP) expression in glial cells in response to neuroinflammatory stimuli. J. Neuroinflammation 8:61 [Google Scholar]
  92. Mohri I, Taniike M, Taniguchi H, Kanekiyo T, Aritake K. 92.  et al. 2006. Prostaglandin D2-mediated microglia/astrocyte interaction enhances astrogliosis and demyelination in twitcher. . J. Neurosci. 26:4383–93 [Google Scholar]
  93. Kranich J, Krautler NJ, Falsig J, Ballmer B, Li S. 93.  et al. 2010. Engulfment of cerebral apoptotic bodies controls the course of prion disease in a mouse strain-dependent manner. J. Exp. Med. 207:2271–81 [Google Scholar]
  94. Walker LC, Jucker M. 94.  2015. Neurodegenerative diseases: expanding the prion concept. Annu. Rev. Neurosci. 38:87–103 [Google Scholar]
  95. De Strooper B, Karran E. 95.  2016. The cellular phase of Alzheimer's disease. Cell 164:603–15 [Google Scholar]
  96. Basso M, Bonetto V. 96.  2016. Extracellular vesicles and a novel form of communication in the brain. Front. Neurosci. 10:127 [Google Scholar]
  97. Brites D, Fernandes A. 97.  2015. Neuroinflammation and depression: microglia activation, extracellular microvesicles and microRNA dysregulation. Front. Cell. Neurosci. 9:476 [Google Scholar]
  98. Zhu C, Herrmann US, Falsig J, Abakumova I, Nuvolone M. 98.  et al. 2016. A neuroprotective role for microglia in prion diseases. J. Exp. Med. 213:1047–59 [Google Scholar]
  99. Hughes MM, Field RH, Perry VH, Murray CL, Cunningham C. 99.  2010. Microglia in the degenerating brain are capable of phagocytosis of beads and of apoptotic cells, but do not efficiently remove PrPSc, even upon LPS stimulation. Glia 58:2017–30 [Google Scholar]
  100. Tanzi RE. 100.  2012. The genetics of Alzheimer disease. Cold Spring Harb. Perspect. Med. 2:a006296 [Google Scholar]
  101. Hyman BT, Holtzman DM. 101.  2015. Apolipoprotein E levels and Alzheimer risk. Ann. Neurol. 77:204–5 [Google Scholar]
  102. Terwel D, Steffensen KR, Verghese PB, Kummer MP, Gustafsson JA. 102.  et al. 2011. Critical role of astroglial apolipoprotein E and liver X receptor-α expression for microglial Aβ phagocytosis. J. Neurosci. 31:7049–59 [Google Scholar]
  103. Cramer PE, Cirrito JR, Wesson DW, Lee CY, Karlo JC. 103.  et al. 2012. ApoE-directed therapeutics rapidly clear beta-amyloid and reverse deficits in AD mouse models. Science 335:1503–6 [Google Scholar]
  104. Mandrekar-Colucci S, Karlo JC, Landreth GE. 104.  2012. Mechanisms underlying the rapid peroxisome proliferator-activated receptor-gamma-mediated amyloid clearance and reversal of cognitive deficits in a murine model of Alzheimer's disease. J. Neurosci. 32:10117–28 [Google Scholar]
  105. El Khoury JB, Moore KJ, Means TK, Leung J, Terada K. 105.  et al. 2003. CD36 mediates the innate host response to β-amyloid. J. Exp. Med. 197:1657–66 [Google Scholar]
  106. Heneka MT, Kummer MP, Stutz A, Delekate A, Schwartz S. 106.  et al. 2013. NLRP3 is activated in Alzheimer's disease and contributes to pathology in APP/PS1 mice. Nature 493:674–78 [Google Scholar]
  107. Guerreiro R, Wojtas A, Bras J, Carrasquillo M, Rogaeva E. 107.  et al. 2013. TREM2 variants in Alzheimer's disease. N. Engl. J. Med. 368:117–27 [Google Scholar]
  108. Jonsson T, Stefansson H, Steinberg S, Jonsdottir I, Jonsson PV. 108.  et al. 2013. Variant of TREM2 associated with the risk of Alzheimer's disease. N. Engl. J. Med. 368:107–16 [Google Scholar]
  109. Bertram L, Lange C, Mullin K, Parkinson M, Hsiao M. 109.  et al. 2008. Genome-wide association analysis reveals putative Alzheimer's disease susceptibility loci in addition to APOE. Am. J. Hum. Genet. 83:623–32 [Google Scholar]
  110. Lambert JC, Heath S, Even G, Campion D, Sleegers K. 110.  et al. 2009. Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer's disease. Nat. Genet. 41:1094–99 [Google Scholar]
  111. Ford JW, McVicar DW. 111.  2009. TREM and TREM-like receptors in inflammation and disease. Curr. Opin. Immunol. 21:38–46 [Google Scholar]
  112. Xing J, Titus AR, Humphrey MB. 112.  2015. The TREM2-DAP12 signaling pathway in Nasu-Hakola disease: a molecular genetics perspective. Res. Rep. Biochem. 5:89–100 [Google Scholar]
  113. Peng Q, Malhotra S, Torchia JA, Kerr WG, Coggeshall KM, Humphrey MB. 113.  2010. TREM2- and DAP12-dependent activation of PI3K requires DAP10 and is inhibited by SHIP1. Sci. Signal. 3:ra38 [Google Scholar]
  114. Wang Y, Cella M, Mallinson K, Ulrich JD, Young KL. 114.  et al. 2015. TREM2 lipid sensing sustains the microglial response in an Alzheimer's disease model. Cell 160:1061–71 [Google Scholar]
  115. Song W, Hooli B, Mullin K, Jin SC, Cella M. 115.  et al. 2016. Alzheimer's disease-associated TREM2 variants exhibit either decreased or increased ligand-dependent activation. Alzheimers Dement In press. https://doi.org/10.1016/j.jalz.2016.07.004 [Google Scholar]
  116. Yeh FL, Wang Y, Tom I, Gonzalez LC, Sheng M. 116.  2016. TREM2 binds to apolipoproteins, including APOE and CLU/APOJ, and thereby facilitates uptake of amyloid-beta by microglia. Neuron 91:328–40 [Google Scholar]
  117. Atagi Y, Liu CC, Painter MM, Chen XF, Verbeeck C. 117.  et al. 2015. Apolipoprotein E is a ligand for triggering receptor expressed on myeloid cells 2 (TREM2). J. Biol. Chem. 290:26043–50 [Google Scholar]
  118. Bailey CC, DeVaux LB, Farzan M. 118.  2015. The triggering receptor expressed on myeloid cells 2 binds apolipoprotein E. J. Biol. Chem. 290:26033–42 [Google Scholar]
  119. Otero K, Turnbull IR, Poliani PL, Vermi W, Cerutti E. 119.  et al. 2009. Macrophage colony-stimulating factor induces the proliferation and survival of macrophages via a pathway involving DAP12 and beta-catenin. Nat. Immunol. 10:734–43 [Google Scholar]
  120. Hsieh CL, Koike M, Spusta SC, Niemi EC, Yenari M. 120.  et al. 2009. A role for TREM2 ligands in the phagocytosis of apoptotic neuronal cells by microglia. J. Neurochem. 109:1144–56 [Google Scholar]
  121. Takahashi K, Prinz M, Stagi M, Chechneva O, Neumann H. 121.  2007. TREM2-transduced myeloid precursors mediate nervous tissue debris clearance and facilitate recovery in an animal model of multiple sclerosis. PLOS Med 4:e124 [Google Scholar]
  122. Takahashi K, Rochford CD, Neumann H. 122.  2005. Clearance of apoptotic neurons without inflammation by microglial triggering receptor expressed on myeloid cells-2. J. Exp. Med. 201:647–57 [Google Scholar]
  123. Turnbull IR, Gilfillan S, Cella M, Aoshi T, Miller M. 123.  et al. 2006. Cutting edge: TREM-2 attenuates macrophage activation. J. Immunol. 177:3520–24 [Google Scholar]
  124. Hamerman JA, Jarjoura JR, Humphrey MB, Nakamura MC, Seaman WE, Lanier LL. 124.  2006. Cutting edge: inhibition of TLR and FcR responses in macrophages by triggering receptor expressed on myeloid cells (TREM)-2 and DAP12. J. Immunol. 177:2051–55 [Google Scholar]
  125. Kober DL, Alexander-Brett JM, Karch CM, Cruchaga C, Colonna M. 125.  et al. 2016. Neurodegenerative disease mutations in TREM2 reveal a functional surface and distinct loss-of-function mechanisms. eLife 5:e20391 [Google Scholar]
  126. Paloneva J, Manninen T, Christman G, Hovanes K, Mandelin J. 126.  et al. 2002. Mutations in two genes encoding different subunits of a receptor signaling complex result in an identical disease phenotype. Am. J. Hum. Genet. 71:656–62 [Google Scholar]
  127. Paloneva J, Autti T, Hakola P, Haltia MJ. 127.  2002. Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL) GeneReviews, updated Mar. 12, 2015, Univ. Wash., Seattle. https://www.ncbi.nlm.nih.gov/books/NBK1197/ [Google Scholar]
  128. Ulrich JD, Finn MB, Wang Y, Shen A, Mahan TE. 128.  et al. 2014. Altered microglial response to Aβ plaques in APPPS1-21 mice heterozygous for TREM2. Mol. Neurodegener. 9:20 [Google Scholar]
  129. Jay TR, Miller CM, Cheng PJ, Graham LC, Bemiller S. 129.  et al. 2015. TREM2 deficiency eliminates TREM2+ inflammatory macrophages and ameliorates pathology in Alzheimer's disease mouse models. J. Exp. Med. 212:287–95 [Google Scholar]
  130. Wang Y, Ulland TK, Ulrich JD, Song W, Tzaferis JA. 130.  et al. 2016. TREM2-mediated early microglial response limits diffusion and toxicity of amyloid plaques. J. Exp. Med. 213:667–75 [Google Scholar]
  131. Yuan P, Condello C, Keene CD, Wang Y, Bird TD. 131.  et al. 2016. TREM2 haplodeficiency in mice and humans impairs the microglia barrier function leading to decreased amyloid compaction and severe axonal dystrophy. Neuron 90:724–39 [Google Scholar]
  132. Jay TR, Hirsch AM, Broihier ML, Miller CM, Neilson LE. 132.  et al. 2017. Disease progression-dependent effects of TREM2 deficiency in a mouse model of Alzheimer's disease. J. Neurosci. 37:637–47 [Google Scholar]
  133. Kleinberger G, Yamanishi Y, Suarez-Calvet M, Czirr E, Lohmann E. 133.  et al. 2014. TREM2 mutations implicated in neurodegeneration impair cell surface transport and phagocytosis. Sci. Transl. Med. 6:243ra86 [Google Scholar]
  134. Wunderlich P, Glebov K, Kemmerling N, Tien NT, Neumann H, Walter J. 134.  2013. Sequential proteolytic processing of the triggering receptor expressed on myeloid cells-2 (TREM2) protein by ectodomain shedding and gamma-secretase-dependent intramembranous cleavage. J. Biol. Chem. 288:33027–36 [Google Scholar]
  135. Suarez-Calvet M, Kleinberger G, Araque Caballero MA, Brendel M, Rominger A. 135.  et al. 2016. sTREM2 cerebrospinal fluid levels are a potential biomarker for microglia activity in early-stage Alzheimer's disease and associate with neuronal injury markers. EMBO Mol. Med. 8:466–76 [Google Scholar]
  136. Piccio L, Deming Y, Del-Aguila JL, Ghezzi L, Holtzman DM. 136.  et al. 2016. Cerebrospinal fluid soluble TREM2 is higher in Alzheimer disease and associated with mutation status. Acta Neuropathol 131:925–33 [Google Scholar]
  137. Bradshaw EM, Chibnik LB, Keenan BT, Ottoboni L, Raj T. 137.  et al. 2013. CD33 Alzheimer's disease locus: altered monocyte function and amyloid biology. Nat. Neurosci. 16:848–50 [Google Scholar]
  138. Griciuc A, Serrano-Pozo A, Parrado AR, Lesinski AN, Asselin CN. 138.  et al. 2013. Alzheimer's disease risk gene CD33 inhibits microglial uptake of amyloid beta. Neuron 78:631–43 [Google Scholar]
  139. Hong S, Beja-Glasser VF, Nfonoyim BM, Frouin A, Li S. 139.  et al. 2016. Complement and microglia mediate early synapse loss in Alzheimer mouse models. Science 352:712–16 [Google Scholar]
  140. Britschgi M, Takeda-Uchimura Y, Rockenstein E, Johns H, Masliah E, Wyss-Coray T. 140.  2012. Deficiency of terminal complement pathway inhibitor promotes neuronal Tau pathology and degeneration in mice. J. Neuroinflammation 9:220 [Google Scholar]
  141. Killick R, Hughes TR, Morgan BP, Lovestone S. 141.  2013. Deletion of Crry, the murine ortholog of the sporadic Alzheimer's disease risk gene CR1, impacts Tau phosphorylation and brain CFH. Neurosci. Lett. 533:96–99 [Google Scholar]
  142. Fonseca MI, Chu S, Pierce AL, Brubaker WD, Hauhart RE. 142.  et al. 2016. Analysis of the putative role of CR1 in Alzheimer's disease: genetic association, expression and function. PLOS One 11:e0149792 [Google Scholar]
  143. Simard AR, Soulet D, Gowing G, Julien JP, Rivest S. 143.  2006. Bone marrow-derived microglia play a critical role in restricting senile plaque formation in Alzheimer's disease. Neuron 49:489–502 [Google Scholar]
  144. El Khoury J, Toft M, Hickman SE, Means TK, Terada K. 144.  et al. 2007. Ccr2 deficiency impairs microglial accumulation and accelerates progression of Alzheimer-like disease. Nat. Med. 13:432–38 [Google Scholar]
  145. Hawkes CA, McLaurin J. 145.  2009. Selective targeting of perivascular macrophages for clearance of beta-amyloid in cerebral amyloid angiopathy. PNAS 106:1261–66 [Google Scholar]
  146. Mildner A, Schmidt H, Nitsche M, Merkler D, Hanisch UK. 146.  et al. 2007. Microglia in the adult brain arise from Ly-6ChiCCR2+ monocytes only under defined host conditions. Nat. Neurosci. 10:1544–53 [Google Scholar]
  147. Ajami B, Bennett JL, Krieger C, Tetzlaff W, Rossi FM. 147.  2007. Local self-renewal can sustain CNS microglia maintenance and function throughout adult life. Nat. Neurosci. 10:1538–43 [Google Scholar]
  148. Renton AE, Chio A, Traynor BJ. 148.  2014. State of play in amyotrophic lateral sclerosis genetics. Nat. Neurosci. 17:17–23 [Google Scholar]
  149. Beers DR, Henkel JS, Xiao Q, Zhao W, Wang J. 149.  et al. 2006. Wild-type microglia extend survival in PU.1 knockout mice with familial amyotrophic lateral sclerosis. PNAS 103:16021–26 [Google Scholar]
  150. Boillee S, Yamanaka K, Lobsiger CS, Copeland NG, Jenkins NA. 150.  et al. 2006. Onset and progression in inherited ALS determined by motor neurons and microglia. Science 312:1389–92 [Google Scholar]
  151. Frakes AE, Ferraiuolo L, Haidet-Phillips AM, Schmelzer L, Braun L. 151.  et al. 2014. Microglia induce motor neuron death via the classical NF-κB pathway in amyotrophic lateral sclerosis. Neuron 81:1009–23 [Google Scholar]
  152. Butovsky O, Siddiqui S, Gabriely G, Lanser AJ, Dake B. 152.  et al. 2012. Modulating inflammatory monocytes with a unique microRNA gene signature ameliorates murine ALS. J. Clin. Investig. 122:3063–87 [Google Scholar]
  153. O'Rourke JG, Bogdanik L, Yanez A, Lall D, Wolf AJ. 153.  et al. 2016. C9orf72 is required for proper macrophage and microglial function in mice. Science 351:1324–29 [Google Scholar]
  154. Lewis CA, Manning J, Rossi F, Krieger C. 154.  2012. The neuroinflammatory response in ALS: the roles of microglia and T cells. Neurol. Res. Int 2012:803701 [Google Scholar]
  155. Cady J, Koval ED, Benitez BA, Zaidman C, Jockel-Balsarotti J. 155.  et al. 2014. TREM2 variant p.R47H as a risk factor for sporadic amyotrophic lateral sclerosis. JAMA Neurol 71:449–53 [Google Scholar]
  156. Cirulli ET, Lasseigne BN, Petrovski S, Sapp PC, Dion PA. 156.  et al. 2015. Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways. Science 347:1436–41 [Google Scholar]
  157. Ahmad L, Zhang SY, Casanova JL, Sancho-Shimizu V. 157.  2016. Human TBK1: a gatekeeper of neuroinflammation. Trends Mol. Med. 22:511–27 [Google Scholar]
  158. Daniele SG, Beraud D, Davenport C, Cheng K, Yin H, Maguire-Zeiss KA. 158.  2015. Activation of MyD88-dependent TLR1/2 signaling by misfolded alpha-synuclein, a protein linked to neurodegenerative disorders. Sci. Signal. 8:ra45 [Google Scholar]
  159. Kumaran R, Cookson MR. 159.  2015. Pathways to Parkinsonism Redux: convergent pathobiological mechanisms in genetics of Parkinson's disease. Hum. Mol. Genet. 24:R32–44 [Google Scholar]
  160. Daher JP, Volpicelli-Daley LA, Blackburn JP, Moehle MS, West AB. 160.  2014. Abrogation of alpha-synuclein-mediated dopaminergic neurodegeneration in LRRK2-deficient rats. PNAS 111:9289–94 [Google Scholar]
  161. Rayaprolu S, Mullen B, Baker M, Lynch T, Finger E. 161.  et al. 2013. TREM2 in neurodegeneration: evidence for association of the p.R47H variant with frontotemporal dementia and Parkinson's disease. Mol. Neurodegener. 8:19 [Google Scholar]
  162. Cardona AE, Pioro EP, Sasse ME, Kostenko V, Cardona SM. 162.  et al. 2006. Control of microglial neurotoxicity by the fractalkine receptor. Nat. Neurosci. 9:917–24 [Google Scholar]
  163. Ellrichmann G, Reick C, Saft C, Linker RA. 163.  2013. The role of the immune system in Huntington's disease. Clin. Dev. Immunol 2013:541259 [Google Scholar]
  164. Tai YF, Pavese N, Gerhard A, Tabrizi SJ, Barker RA. 164.  et al. 2007. Microglial activation in presymptomatic Huntington's disease gene carriers. Brain 130:1759–66 [Google Scholar]
  165. Miller JR, Lo KK, Andre R, Hensman Moss DJ, Trager U. 165.  et al. 2016. RNA-Seq of Huntington's disease patient myeloid cells reveals innate transcriptional dysregulation associated with proinflammatory pathway activation. Hum. Mol. Genet. 25:2893–904 [Google Scholar]
  166. Connolly C, Magnusson-Lind A, Lu G, Wagner PK, Southwell AL. 166.  et al. 2016. Enhanced immune response to MMP3 stimulation in microglia expressing mutant huntingtin. Neuroscience 325:74–88 [Google Scholar]
  167. Miller JP, Holcomb J, Al-Ramahi I, de Haro M, Gafni J. 167.  et al. 2010. Matrix metalloproteinases are modifiers of huntingtin proteolysis and toxicity in Huntington's disease. Neuron 67:199–212 [Google Scholar]
  168. Quigley HA. 168.  2011. Glaucoma. Lancet 377:1367–77 [Google Scholar]
  169. Nussenblatt RB, Liu B, Li Z. 169.  2009. Age-related macular degeneration: an immunologically driven disease. Curr. Opin. Investig. Drugs 10:434–42 [Google Scholar]
  170. Vohra R, Tsai JC, Kolko M. 170.  2013. The role of inflammation in the pathogenesis of glaucoma. Surv. Ophthalmol. 58:311–20 [Google Scholar]
  171. Buschini E, Piras A, Nuzzi R, Vercelli A. 171.  2011. Age related macular degeneration and drusen: neuroinflammation in the retina. Prog. Neurobiol. 95:14–25 [Google Scholar]
  172. Karlstetter M, Ebert S, Langmann T. 172.  2010. Microglia in the healthy and degenerating retina: insights from novel mouse models. Immunobiology 215:685–91 [Google Scholar]
  173. Bringmann A, Wiedemann P. 173.  2012. Muller glial cells in retinal disease. Ophthalmologica 227:1–19 [Google Scholar]
  174. Madeira MH, Boia R, Elvas F, Martins T, Cunha RA. 174.  et al. 2016. Selective A2A receptor antagonist prevents microglia-mediated neuroinflammation and protects retinal ganglion cells from high intraocular pressure-induced transient ischemic injury. Transl. Res. 169:112–28 [Google Scholar]
  175. Chen SK, Tvrdik P, Peden E, Cho S, Wu S. 175.  et al. 2010. Hematopoietic origin of pathological grooming in Hoxb8 mutant mice. Cell 141:775–85 [Google Scholar]
  176. Yasui DH, Xu H, Dunaway KW, Lasalle JM, Jin LW, Maezawa I. 176.  2013. MeCP2 modulates gene expression pathways in astrocytes. Mol. Autism 4:3 [Google Scholar]
  177. Cronk JC, Derecki NC, Ji E, Xu Y, Lampano AE. 177.  et al. 2015. Methyl-CpG binding protein 2 regulates microglia and macrophage gene expression in response to inflammatory stimuli. Immunity 42:679–91 [Google Scholar]
  178. Derecki NC, Cronk JC, Lu Z, Xu E, Abbott SB. 178.  et al. 2012. Wild-type microglia arrest pathology in a mouse model of Rett syndrome. Nature 484:105–9 [Google Scholar]
  179. Wang J, Wegener JE, Huang TW, Sripathy S, De Jesus-Cortes H. 179.  et al. 2015. Wild-type microglia do not reverse pathology in mouse models of Rett syndrome. Nature 521:E1–4 [Google Scholar]
  180. Schafer DP, Heller CT, Gunner G, Heller M, Gordon C. 180.  et al. 2016. Microglia contribute to circuit defects in Mecp2 null mice independent of microglia-specific loss of Mecp2 expression. eLife 5:e15224 [Google Scholar]
  181. Steiner J, Bielau H, Brisch R, Danos P, Ullrich O. 181.  et al. 2008. Immunological aspects in the neurobiology of suicide: elevated microglial density in schizophrenia and depression is associated with suicide. J. Psychiatr. Res. 42:151–57 [Google Scholar]
  182. Steiner J, Walter M, Gos T, Guillemin GJ, Bernstein HG. 182.  et al. 2011. Severe depression is associated with increased microglial quinolinic acid in subregions of the anterior cingulate gyrus: evidence for an immune-modulated glutamatergic neurotransmission?. J. Neuroinflammation 8:94 [Google Scholar]
  183. Torres-Platas SG, Cruceanu C, Chen GG, Turecki G, Mechawar N. 183.  2014. Evidence for increased microglial priming and macrophage recruitment in the dorsal anterior cingulate white matter of depressed suicides. Brain Behav. Immun. 42:50–59 [Google Scholar]
  184. Dantzer R, O'Connor JC, Freund GG, Johnson RW, Kelley KW. 184.  2008. From inflammation to sickness and depression: when the immune system subjugates the brain. Nat. Rev. Neurosci. 9:46–56 [Google Scholar]
  185. Yirmiya R, Rimmerman N, Reshef R. 185.  2015. Depression as a microglial disease. Trends Neurosci 38:637–58 [Google Scholar]
  186. Shinjo R, Imagama S, Ito Z, Ando K, Nishida Y. 186.  et al. 2014. Keratan sulfate expression is associated with activation of a subpopulation of microglia/macrophages in Wallerian degeneration. Neurosci. Lett. 579:80–85 [Google Scholar]
  187. Doty KR, Guillot-Sestier MV, Town T. 187.  2015. The role of the immune system in neurodegenerative disorders: Adaptive or maladaptive?. Brain Res 1617:155–73 [Google Scholar]
  188. Wisniewski T, Goni F. 188.  2015. Immunotherapeutic approaches for Alzheimer's disease. Neuron 85:1162–76 [Google Scholar]
  189. Sevigny J, Chiao P, Bussière T, Weinreb PH, Williams L. 189.  et al. 2016. The antibody aducanumab reduces Aβ plaques in Alzheimer's disease. Nature 537:50–56 [Google Scholar]
  190. Xiang X, Werner G, Bohrmann B, Liesz A, Mazaheri F. 190.  et al. 2016. TREM2 deficiency reduces the efficacy of immunotherapeutic amyloid clearance. EMBO Mol. Med. 8:992–1004 [Google Scholar]
  191. Spangenberg EE, Green KN. 191.  2017. Inflammation in Alzheimer's disease: lessons learned from microglia-depletion models. Brain Behav. Immun. 61:1–11 [Google Scholar]
  192. Olmos-Alonso A, Schetters ST, Sri S, Askew K, Mancuso R. 192.  et al. 2016. Pharmacological targeting of CSF1R inhibits microglial proliferation and prevents the progression of Alzheimer's-like pathology. Brain 139:891–907 [Google Scholar]
  193. Chitu V, Gokhan S, Gulinello M, Branch CA, Patil M. 193.  et al. 2015. Phenotypic characterization of a Csf1r haploinsufficient mouse model of adult-onset leukodystrophy with axonal spheroids and pigmented glia (ALSP). Neurobiol. Dis. 74:219–28 [Google Scholar]
  194. Luo J, Elwood F, Britschgi M, Villeda S, Zhang H. 194.  et al. 2013. Colony-stimulating factor 1 receptor (CSF1R) signaling in injured neurons facilitates protection and survival. J. Exp. Med. 210:157–72 [Google Scholar]
  195. Daneschvar HL, Aronson MD, Smetana GW. 195.  2015. Do statins prevent Alzheimer's disease? A narrative review. Eur. J. Intern. Med. 26:666–69 [Google Scholar]
  196. Jin G, Bai D, Yin S, Yang Z, Zou D. 196.  et al. 2016. Silibinin rescues learning and memory deficits by attenuating microglia activation and preventing neuroinflammatory reactions in SAMP8 mice. Neurosci. Lett. 629:256–61 [Google Scholar]
  197. Savage JC, Jay T, Goduni E, Quigley C, Mariani MM. 197.  et al. 2015. Nuclear receptors license phagocytosis by TREM2+ myeloid cells in mouse models of Alzheimer's disease. J. Neurosci. 35:6532–43 [Google Scholar]
  198. Luz I, Liraz O, Michaelson DM. 198.  2016. An anti-apoE4 specific monoclonal antibody counteracts the pathological effects of apoE4 in vivo. Curr. Alzheimer Res. 13:918–29 [Google Scholar]
  199. Nixon RA, Yang DS. 199.  2012. Autophagy and neuronal cell death in neurological disorders. Cold Spring Harb. Perspect. Biol. 4:a008839 [Google Scholar]
  200. Cho MH, Cho K, Kang HJ, Jeon EY, Kim HS. 200.  et al. 2014. Autophagy in microglia degrades extracellular beta-amyloid fibrils and regulates the NLRP3 inflammasome. Autophagy 10:1761–75 [Google Scholar]
  201. Kim HJ, Cho MH, Shim WH, Kim JK, Jeon EY. 201.  et al. 2016. Deficient autophagy in microglia impairs synaptic pruning and causes social behavioral defects. Mol. Psychiatry. In press. https://doi.org/10.1038/mp.2016.103 [Google Scholar]
  202. Varvel NH, Grathwohl SA, Degenhardt K, Resch C, Bosch A. 202.  et al. 2015. Replacement of brain-resident myeloid cells does not alter cerebral amyloid-beta deposition in mouse models of Alzheimer's disease. J. Exp. Med. 212:1803–9 [Google Scholar]
  203. Prokop S, Miller KR, Drost N, Handrick S, Mathur V. 203.  et al. 2015. Impact of peripheral myeloid cells on amyloid-beta pathology in Alzheimer's disease-like mice. J. Exp. Med. 212:1811–18 [Google Scholar]

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error