Interplay between innate immunity and Alzheimer disease: APOE and TREM2 in the spotlight

Nature Reviews. Immunology
Yang Shi, David M Holtzman

Abstract

Alzheimer disease is more than a pure proteopathy. Chronic neuroinflammation stands out during the pathogenesis of the disease and in turn modulates disease progression. The central nervous system (CNS) is separated from the blood circulation by the blood-brain barrier. In Alzheimer disease, neuroinflammation heavily relies on innate immune responses that are primarily mediated by CNS-resident microglia. APOE (which encodes apolipoprotein E) is the strongest genetic risk factor for Alzheimer disease, and APOE was recently shown to affect the disease in part through its immunomodulatory function. This function of APOE is likely linked to triggering receptor expressed on myeloid cells 2 (TREM2), which is expressed by microglia in the CNS. Here, we review the rapidly growing literature on the role of disease-associated microglia, TREM2 and APOE in the pathogenesis of Alzheimer disease and present an integrated view of innate immune function in Alzheimer disease.

References

Jul 28, 1995·Neuroscience Letters·T UchiharaJ J Hauw
Nov 8, 1994·Proceedings of the National Academy of Sciences of the United States of America·W J StrittmatterA D Roses
Oct 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·D E SchmechelA D Roses
Mar 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·W J StrittmatterA D Roses
Apr 1, 1996·Experimental Neurology·L M FlemingG V Johnson
Jan 29, 2000·Immunology and Cell Biology·M A de Pablo, G Alvarez de Cienfuegos
Mar 1, 2000·Proceedings of the National Academy of Sciences of the United States of America·D M HoltzmanS M Paul
Jul 12, 2001·Proceedings of the National Academy of Sciences of the United States of America·Y HuangR W Mahley
Sep 13, 2001·The European Journal of Neuroscience·X QiaoS M Paul
Feb 26, 2004·Neuron·José Luis Marín-TevaMichel Mallat
Mar 12, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Walter J BrechtYadong Huang
Feb 25, 2005·The Journal of Experimental Medicine·Kazuya TakahashiHarald Neumann
May 17, 2005·Nature Neuroscience·Dimitrios DavalosWen-Biao Gan
Sep 30, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Masashi KitazawaFrank M LaFerla
Nov 21, 2007·Nature Neuroscience·Bahareh AjamiFabio M V Rossi
Dec 18, 2007·Cell·Beth StevensBen A Barres
Dec 25, 2007·Neurobiology of Aging·Michael P VitekCarol A Colton
Feb 26, 2008·Nature Neuroscience·Gilbert GallardoThomas C Südhof
Jul 8, 2008·Nature Immunology·Annett HalleDouglas T Golenbock
Aug 8, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Shirley WakselmanAlain Bessis
Nov 26, 2008·Nature Reviews. Immunology·David M Mosser, Justin P Edwards
Jan 24, 2009·Proceedings of the National Academy of Sciences of the United States of America·Federica AgostaMaria Luisa Gorno-Tempini
Oct 15, 2009·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Paramita ChakrabartyPritam Das
Oct 20, 2009·Nature Neuroscience·Stefan A GrathwohlMathias Jucker
Jan 20, 2010·Lancet Neurology·Clifford R JackJohn Q Trojanowski
Apr 7, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Paramita ChakrabartyPritam Das
Apr 8, 2010·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Tomomi KiyotaTsuneya Ikezu
Jul 27, 2010·Current Opinion in Neurobiology·Ye Zhang, Ben A Barres
Oct 6, 2010·Neuron·Kiran BhaskarBruce T Lamb
Feb 18, 2011·Molecular Neurodegeneration·Paramita ChakrabartyTodd E Golde
Apr 30, 2011·Physiological Reviews·Helmut KettenmannAlexei Verkhratsky
Jul 1, 2011·Science Translational Medicine·Joseph M CastellanoDavid M Holtzman
Jul 23, 2011·Science·Rosa C PaolicelliCornelius T Gross
Aug 4, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Michael B Fessler, John S Parks
Aug 16, 2011·Immunobiology·Helen CrehanJohn Hardy

❮ Previous
Next ❯

Citations

Apr 6, 2019·Acta Neuropathologica·Steven EstusDavid W Fardo
Jul 7, 2019·Acta Neuropathologica Communications·Thomas VogelsTomáš Hromádka
Jul 23, 2019·Medicinal Research Reviews·Lili ZhangRongbiao Pi
Aug 9, 2019·PLoS Pathogens·Luhua Qiao, Guangxiang George Luo
May 29, 2019·Movement Disorders : Official Journal of the Movement Disorder Society·Jared T HinkleTed M Dawson
Feb 2, 2019·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Mariko SaitoBhaskar C Das
Jun 21, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Liang ShengGuangxu Xu
Mar 19, 2020·International Journal of Molecular Sciences·Masashi TanakaMasafumi Ihara
Jun 13, 2019·Molecular Neurodegeneration·Ramsey NajmYadong Huang
Jun 10, 2020·Annals of Clinical and Translational Neurology·Fen HuangJames D Berry
Apr 22, 2020·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Shuichi TonomuraRobert P Friedland
Nov 19, 2019·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Dong-Oh Seo, David M Holtzman
Jul 10, 2019·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Yongzhen MiaoFang Zhang
Aug 20, 2020·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Courtney K Walker, Jeremy H Herskowitz
Sep 5, 2020·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Pyry N SipiläMika Kivimäki
Oct 12, 2019·The Journal of Experimental Medicine·Yang ShiDavid M Holtzman
Dec 28, 2018·International Journal of Molecular Sciences·Cody M WolfeRadosveta Koldamova
Feb 16, 2020·Journal of Neuroinflammation·Neta LaxTamir Ben-Hur
Dec 12, 2019·Frontiers in Neuroscience·Liam GraciaUmesh K Jinwal
Jul 3, 2020·Nature Reviews. Drug Discovery·Kimberly Scearce-LevieJoseph W Lewcock
Jun 20, 2020·Journal of Neuroinflammation·Man Ying WongWenjie Luo
Sep 10, 2020·Journal of Personalized Medicine·Chiara ArgentatiSabata Martino
Sep 11, 2020·Molecular Neurodegeneration·Joanna E PankiewiczMartin J Sadowski
Sep 24, 2020·International Journal of Molecular Sciences·Juan Antonio Garcia-LeonAntonia Gutierrez
Dec 12, 2018·Frontiers in Aging Neuroscience·Honghua ZhengYun-Wu Zhang
Jan 16, 2019·Cold Spring Harbor Symposia on Quantitative Biology·Scott A Small, Larry W Swanson
Oct 9, 2019·Translational Psychiatry·Gaurav JainAndre Fischer
Jan 8, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Simone BrioschiMarco Colonna
Sep 17, 2019·Journal of Alzheimer's Disease : JAD·Kalicharan PatraHenrietta M Nielsen
Feb 13, 2020·Current Alzheimer Research·Patrick Süß, Johannes C M Schlachetzki
May 14, 2020·Nature Communications·Ju Youn LeeJae-Sung Bae
Dec 12, 2019·Frontiers in Cellular Neuroscience·Mathilde CherayKathleen Grabert
Feb 11, 2020·Frontiers in Aging Neuroscience·Li Zhong, Xiao-Fen Chen

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Methods Mentioned

BETA
antisense oligonucleotides

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