title: TREM2 Function in Alzheimer's Disease and Neurodegeneration.
abstract: Alzheimer's disease (AD), the most common cause of dementia in the elderly, is a complex neurodegenerative disease marked by the appearance of amyloid-β (Aβ) plaques and hyperphosphorylated tau tangles. Alzheimer's disease has a strong genetic component, and recent advances in genome technology have unearthed novel variants in several genes, which could provide insight into the pathogenic mechanisms that contribute to AD. Particularly interesting are variants in the microglial-expressed receptor TREM2 which are associated with a 2-4-fold increased risk of developing AD. Since the discovery of a link between TREM2 and AD, multiple studies have emerged testing whether partial or complete loss of TREM2 function contributed to Aβ deposition or Aβ-associated microgliosis. Although some confounding conflicting data have emerged from these studies regarding the role of TREM2 in regulating Aβ deposition within the hippocampus, the most consistent and striking observation is a strong decrease in microgliosis surrounding Aβ plaques in TREM2 haploinsufficient and TREM2 deficient mice. Interestingly, a similar impairment in microgliosis has been reported in mouse models of prion disease, stroke, and multiple sclerosis, suggesting a critical role for TREM2 in supporting microgliosis in response to pathology in the central nervous system. In this Review, we summarize recent reports on the role of TREM2 in AD pathology and hypothesized mechanisms by which TREM2 function could influence AD-induced microgliosis.
authors: Department of Neurology, Knight Alzheimer's Disease Research Center, and Hope Center for Neurological Disorders, Washington University School of Medicine , St. Louis, Missouri 63110, United States.
authors: Jason D
authors: JD
authors: Ulrich
authors: Department of Neurology, Knight Alzheimer's Disease Research Center, and Hope Center for Neurological Disorders, Washington University School of Medicine , St. Louis, Missouri 63110, United States.
authors: David M
authors: DM
authors: Holtzman
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D002490:Central Nervous System / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D017628:Microglia / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000378:metabolism*; D058225:Plaque, Amyloid / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*
chemical_list: D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; C498715:TREM2 protein, human
keywords: Alzheimer’s disease; TREM2; amyloid-β; apolipoprotein E; microglia; neurodegeneration