Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model.

ABSTRACT: TREM2 is an Alzheimer's disease (AD) risk gene expressed in microglia. To study the role of Trem2 in a mouse model of β-amyloidosis, we compared PS2APP transgenic mice versus PS2APP mice lacking Trem2 (PS2APP;Trem2^ko) at ages ranging from 4 to 22 months. Microgliosis was impaired in PS2APP;Trem2^ko mice, with Trem2-deficient microglia showing compromised expression of proliferation/Wnt-related genes and marked accumulation of ApoE. Plaque abundance was elevated in PS2APP;Trem2^ko females at 6-7 months; but by 12 or 19-22 months of age, it was notably diminished in female and male PS2APP;Trem2^ko mice, respectively. Across all ages, plaque morphology was more diffuse in PS2APP;Trem2^ko brains, and the Aβ42:Aβ40 r

SUBMITTER: Meilandt WJ 

PROVIDER: S-EPMC7046459 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature