TREM2-Dependent Effects on Microglia in Alzheimer's Disease

Frontiers in Aging Neuroscience
Yingyue ZhouMarco Colonna

Abstract

Alzheimer's disease (AD) is a late-onset dementia characterized by the deposition of amyloid plaques and formation of neurofibrillary tangles (NFTs) which lead to neuronal loss and cognitive deficits. Abnormal protein aggregates in the AD brain are also associated with reactive microglia and astrocytes. Whether this glial response is beneficial or detrimental in AD pathology is under debate. Microglia are the resident innate immune cells in the central nervous system (CNS) that survey the surrounding environment. Genome-wide association studies (GWAS) have identified the R47H variant of triggering receptor expressed on myeloid cell 2 (TREM2) as a risk factor for late-onset AD (LOAD) with an odds ratio of 4.5. TREM2 is an immunoreceptor primarily present on microglia in the CNS that binds to polyanionic molecules. The transmembrane domain of TREM2 signals through DAP12, an adaptor protein that contains an immunoreceptor tyrosine-based activation motif (ITAM), which mediates TREM2 signaling and promotes microglial activation and survival. In mouse models of AD, Trem2 haplodeficiency and deficiency lead to reduced microglial clustering around amyloid β (Aβ) plaques, suggesting TREM2 is required for plaque-associated microglial res...Continue Reading

References

Mar 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·W J StrittmatterA D Roses
Mar 28, 2003·Nature·Nobumasa TakasugiTakeshi Iwatsubo
Jul 9, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Michael R DawsWilliam E Seaman
Feb 25, 2005·The Journal of Experimental Medicine·Kazuya TakahashiHarald Neumann
Feb 14, 2006·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Magdalena SastreMichael Thomas Heneka
Mar 1, 2006·Neurology·Marino Muxfeldt BianchinAmerico Ceiki Sakamoto
Aug 5, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jessica A HamermanLewis L Lanier
Sep 5, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Isaiah R TurnbullMarco Colonna
Dec 18, 2007·Cell·Beth StevensBen A Barres
Jan 28, 2009·The Journal of Cell Biology·Elsa-Noah N'DiayeWilliam E Seaman
Jan 20, 2010·Lancet Neurology·Clifford R JackJohn Q Trojanowski
Feb 11, 2010·Cell·Noboru MizushimaBeth Levine
May 21, 2010·Science Signaling·Qisheng PengMary Beth Humphrey
Oct 20, 2010·Neuron·Lars BertramRudolph E Tanzi
Apr 8, 2011·Science Translational Medicine·David M HoltzmanAlison M Goate
Feb 9, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Karel OteroMarco Colonna
Jul 13, 2012·The New England Journal of Medicine·Randall J BatemanDominantly Inherited Alzheimer Network
Nov 16, 2012·The New England Journal of Medicine·Thorlakur JonssonKari Stefansson
Nov 16, 2012·The New England Journal of Medicine·Rita GuerreiroAlzheimer Genetic Analysis Group
Dec 21, 2012·Nature·Michael Thomas HenekaDouglas T Golenbock
Feb 19, 2014·JAMA Neurology·Janet CadyMatthew B Harms
Jun 5, 2014·Molecular Neurodegeneration·Jason D UlrichDavid M Holtzman
Jun 6, 2014·Human Molecular Genetics·Sheng Chih JinCarlos Cruchaga
Jul 6, 2014·Science Translational Medicine·Gernot KleinbergerChristian Haass
Jul 22, 2014·Neurobiology of Aging·Mathias ThelenAlfredo Ramirez
Sep 19, 2014·Acta Neuropathologica Communications·Gary P MorrisBryce Vissel
Jan 30, 2015·Nature Communications·Carlo CondelloJaime Grutzendler
Apr 22, 2015·The Journal of Experimental Medicine·Kangyun WuMichael J Holtzman
Sep 17, 2015·The Journal of Biological Chemistry·Yuka AtagiGuojun Bu
Feb 26, 2016·Nature Reviews. Neuroscience·Marco Colonna, Yaming Wang
Feb 28, 2016·Brain : a Journal of Neurology·Elizabeth E SpangenbergKim N Green
Apr 20, 2016·The Journal of Experimental Medicine·Yaming WangMarco Colonna
Aug 16, 2016·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Wilbur SongMarco Colonna
Aug 20, 2016·Science·Richard M Ransohoff
Aug 31, 2016·Molecular Psychiatry·A CaccamoS Oddo
Dec 16, 2016·Science Translational Medicine·Marc Suárez-CalvetDominantly Inherited Alzheimer Network
Jan 20, 2017·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Taylor R JayGary E Landreth
Feb 18, 2017·The Journal of Experimental Medicine·Li ZhongGuojun Bu
May 10, 2017·EMBO Reports·Fargol MazaheriChristian Haass
Aug 13, 2017·Cell·Tyler K UllandMarco Colonna
Oct 27, 2017·Proceedings of the National Academy of Sciences of the United States of America·Cheryl E G LeynsDavid M Holtzman
Jan 3, 2018·Nature·Carmen VenegasMichael Thomas Heneka
Jan 13, 2018·The Journal of Experimental Medicine·Wilbur SongMarco Colonna

Citations

Feb 7, 2019·Journal of Leukocyte Biology·Shoutang Wang, Marco Colonna
Jan 22, 2020·Current Alzheimer Research·Keshen Li
Dec 19, 2019·The International Journal of Neuroscience·Qian WangYueran Zhao
Sep 25, 2019·Cells·Gianfranco NataleFrancesco Fornai
Dec 12, 2019·Frontiers in Cellular Neuroscience·Mathilde CherayKathleen Grabert
Dec 12, 2018·Frontiers in Aging Neuroscience·Honghua ZhengYun-Wu Zhang
Oct 2, 2020·Cells·Tuuli-Maria SonninenŠárka Lehtonen
Aug 23, 2020·Cell Death & Disease·Zhaoji LiuYun-Wu Zhang
Dec 15, 2020·The American Journal of Chinese Medicine·Yu-Ling XuYu-Hua Jia
Jan 12, 2021·Obesity Reviews : an Official Journal of the International Association for the Study of Obesity·Andrés A HerradaMatthias Piesche
Dec 17, 2020·International Journal of Molecular Sciences·Daniele LanaMaria Grazia Giovannini
Dec 18, 2020·Frontiers in Aging Neuroscience·Season K Wyatt-Johnson, Randy R Brutkiewicz
Mar 4, 2021·International Journal of Molecular Sciences·Gaia PiccioniRobert Nisticò
Apr 3, 2021·International Journal of Molecular Sciences·Mehdi EshraghiSaeid Ghavami
Jun 9, 2020·Neurobiology of Disease·Amy J Gleichman, S Thomas Carmichael

Methods Mentioned

BETA
lipidation
electron microscopy

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