TREM2, Microglia, and Neurodegenerative Diseases

Trends Mol Med. 2017 Jun;23(6):512-533. doi: 10.1016/j.molmed.2017.03.008. Epub 2017 Apr 22.


Alzheimer's disease (AD) is the most common form of dementia and the 6th leading cause of death in the US. The neuropathological hallmarks of the disease are extracellular amyloid-β (Aβ) plaques and intraneuronal hyperphosphorylated tau aggregates. Genetic variants of TREM2 (triggering receptor expressed on myeloid cells 2), a cell-surface receptor expressed selectively in myeloid cells, greatly increase the risk of AD, implicating microglia and the innate immune system as pivotal factors in AD pathogenesis. Recent studies have advanced our understanding of TREM2 biology and microglial activities in aging and neurodegenerative brains, providing new insights into TREM2 functions in amyloid plaque maintenance, microglial envelopment of plaque, microglia viability, and the identification of novel TREM2 ligands. Our increased understanding of TREM2 and microglia has opened new avenues for therapeutic intervention to delay or prevent the progression of AD.

Keywords: APOE; APOJ; Alzheimer’s disease; Nasu–Hakola disease; PLOSL; TREM2; clusterin; frontotemporal dementia; lipoproteins; microglia; multiple sclerosis; neurodegenerative disease.

Publication types

  • Review

MeSH terms

  • Aging / genetics
  • Aging / immunology*
  • Aging / pathology
  • Alzheimer Disease / epidemiology
  • Alzheimer Disease / genetics
  • Alzheimer Disease / immunology*
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / genetics
  • Amyloid beta-Peptides / immunology
  • Animals
  • Humans
  • Immunity, Innate*
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / immunology*
  • Microglia / immunology*
  • Microglia / pathology
  • Myeloid Cells / immunology*
  • Myeloid Cells / pathology
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / immunology*
  • United States / epidemiology


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