TREM2 dependent and independent functions of microglia in Alzheimer's disease

Mol Neurodegener. 2022 Dec 23;17(1):84. doi: 10.1186/s13024-022-00588-y.

Abstract

Microglia are central players in brain innate immunity and have been the subject of extensive research in Alzheimer's disease (AD). In this review, we aim to summarize the genetic and functional discoveries that have advanced our understanding of microglia reactivity to AD pathology. Given the heightened AD risk posed by rare variants of the microglial triggering receptor expressed on myeloid cells 2 (TREM2), we will focus on the studies addressing the impact of this receptor on microglia responses to amyloid plaques, tauopathy and demyelination pathologies in mouse and human. Finally, we will discuss the implications of recent discoveries on microglia and TREM2 biology on potential therapeutic strategies for AD.

Keywords: APOE; Alzheimer’s disease; Beta-amyloid pathology; Demyelination; Microglia; TREM2; Tauopathy.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease* / pathology
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Brain / metabolism
  • Disease Models, Animal
  • Humans
  • Immunity, Innate
  • Membrane Glycoproteins / genetics
  • Mice
  • Microglia / metabolism
  • Receptors, Immunologic / genetics

Substances

  • Amyloid beta-Peptides
  • TREM2 protein, human
  • Membrane Glycoproteins
  • Receptors, Immunologic
  • Trem2 protein, mouse