Loss of TREM2 diminishes CAA despite an overall increase of amyloid load in Tg-SwDI mice.

ABSTRACT:

Introduction

The microglial receptor triggering receptor expressed on myeloid cells 2 (TREM2) is a major risk factor for Alzheimer's disease (AD). Experimentally, Trem2 deficiency affects parenchymal amyloid beta (Aβ) deposition. However, the role of TREM2 in cerebrovascular amyloidosis, especially cerebral amyloid angiopathy (CAA), remains unexplored.

Methods

Tg-SwDI (SwDI) mice, a CAA-prone model of AD, and Trem2 knockout mice were crossed to generate SwDI/TWT, SwDI/THet, and SwDI/TKO mice, followed by pathological and biochemical analyses at 16 months of age.

Results

Loss of Trem2 led to a dramatic decrease in CAA and microglial association, despite a marked increase in overall brain Aβ load. Single nucleus RNA sequencing analysis revealed that in the absence of Tr

SUBMITTER: Zhong R 

PROVIDER: S-EPMC11567860 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature