TREM2-mediated early microglial response limits diffusion and toxicity of amyloid plaques

Triggering receptor expressed on myeloid cells 2 (TREM2) is a microglial receptor that recognizes changes in the lipid microenvironment, which may occur during amyloid β (Aβ) accumulation and neuronal degeneration in Alzheimer's disease (AD). Rare TREM2 variants that affect TREM2 function lead to an increased risk of developing AD. In murine models of AD, TREM2 deficiency prevents microglial clustering around Aβ deposits. However, the origin of myeloid cells surrounding amyloid and the impact of TREM2 on Aβ accumulation are a matter of debate. Using parabiosis, we found that amyloid-associated myeloid cells derive from brain-resident microglia rather than from recruitment of peripheral blood monocytes. To…

• NM
  National Multiple Sclerosis Society

  Awards: RG4687A1, RG4687A1/1
• EL
  Eli Lilly and Company
• JF
  JPB Foundation

  Awards: 5T32CA009547, RG4687A1/1
• CA
  Cure Alzheimer's Fund
• HC
  Hope Center for Neurological Disorders
• MS
  Multiple Sclerosis Society
• NI
  National Institutes of Health

  Awards: 5T32CA009547, RF1 AG05148501, AG047644, P50 AG005681, AG005681, 5T32CA009547-30
• AD
  Alzheimer's Disease Research Center, Emory University

  Award: P50 AG005681-30
• CF
  Charles F. and Joanne Knight Alzheimer Disease Research Center, Washington University in St. Louis