TREM2 function impedes tau seeding in neuritic plaques

Nat Neurosci. 2019 Aug;22(8):1217-1222. doi: 10.1038/s41593-019-0433-0. Epub 2019 Jun 24.

Abstract

Variants in the triggering receptor expressed on myeloid cells 2 (TREM2) have been associated with increased risk for sporadic, late-onset Alzheimer's disease. Here we show that germline knockout of Trem2 or the TREM2R47H variant reduces microgliosis around amyloid-β plaques and facilitates the seeding and spreading of neuritic plaque tau aggregates. These findings demonstrate a key role for TREM2 and microglia in limiting the development of peri-plaque tau pathologies.

Publication types

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

MeSH terms

  • Animals
  • Cerebral Cortex / pathology
  • Membrane Glycoproteins / genetics*
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Mice, Knockout
  • Microglia / pathology
  • Plaque, Amyloid / genetics*
  • Plaque, Amyloid / metabolism*
  • Receptors, Immunologic / genetics*
  • Receptors, Immunologic / metabolism*
  • Tauopathies / genetics*
  • Tauopathies / metabolism*
  • tau Proteins / genetics*
  • tau Proteins / metabolism*

Substances

  • Membrane Glycoproteins
  • Receptors, Immunologic
  • Trem2 protein, mouse
  • tau Proteins