Homeostatic microglia initially seed and activated microglia later reshape amyloid plaques in Alzheimer's Disease.

ABSTRACT: The role of microglia in the amyloid cascade of Alzheimer's disease (AD) is debated due to conflicting findings. Using a genetic and a pharmacological approach we demonstrate that depletion of microglia before amyloid-β (Aβ) plaque deposition, leads to a reduction in plaque numbers and neuritic dystrophy, confirming their role in plaque initiation. Transplanting human microglia restores Aβ plaque formation. While microglia depletion reduces insoluble Aβ levels, soluble Aβ concentrations stay consistent, challenging the view that microglia clear Aβ. In later stages, microglial depletion decreases plaque compaction and increases neuritic dystrophy, suggesting a protective role. Human microglia with the TREM2^R47H/R47H mutation exacerbate plaque pathology, emphasizing the importance

SUBMITTER: Baligacs N 

PROVIDER: S-EPMC11621353 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature