Loss of TREM2 function increases amyloid seeding but reduces plaque-associated ApoE

Jan 9, 2019Nature neuroscience

Loss of TREM2 function increases early amyloid buildup but lowers ApoE levels near plaques

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Abstract

Coding variants in TREM2 are associated with late-onset Alzheimer's disease.

  • Amyloid plaque seeding increases when Trem2 is not functional.
  • Decreased clustering of microglia is observed around newly formed plaques in Trem2 loss-of-function models.
  • Reduced deposition of apolipoprotein E (ApoE) in plaques correlates with the presence of TREM2 coding variants in Alzheimer's patients.
  • Microglia are identified as a source of plaque-associated ApoE.
  • Longitudinal imaging shows accelerated amyloid formation in early stages without functional Trem2, but progression slows with aging.

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