TREM2 sustains microglial expansion during aging and response to demyelination

Microglia contribute to development, homeostasis, and immunity of the CNS. Like other tissue-resident macrophage populations, microglia express the surface receptor triggering receptor expressed on myeloid cells 2 (TREM2), which binds polyanions, such as dextran sulphate and bacterial LPS, and activates downstream signaling cascades through the adapter DAP12. Individuals homozygous for inactivating mutations in TREM2 exhibit demyelination of subcortical white matter and a lethal early onset dementia known as Nasu-Hakola disease. How TREM2 deficiency mediates demyelination and disease is unknown. Here, we addressed the basis for this genetic association using Trem2(-/-) mice. In WT mice, microglia expanded in…

• EL
  Eli Lilly and Company
• CA
  Cure Alzheimer's Fund
• FC
  Fondazione Cariplo
• NI
  National Institutes of Health

  Awards: DK020579, P50 AG005681, AG005681
• CF
  Charles F. and Joanne Knight Alzheimer Disease Research Center, Washington University in St. Louis
• JS
  Japan Society for the Promotion of Science
• R
  RIKEN