The Trem2 R47H variant confers loss-of-function-like phenotypes in Alzheimer's disease.

ABSTRACT:

Background

The R47H variant of Triggering Receptor Expressed on Myeloid cells 2 (TREM2) confers greatly increased risk for Alzheimer's disease (AD), reflective of a central role for myeloid cells in neurodegeneration. Understanding how this variant confers AD risk promises to provide important insights into how myeloid cells contribute to AD pathogenesis and progression.

Methods

In order to investigate this mechanism, CRISPR/Cas9 was used to generate a mouse model of AD harboring one copy of the single nucleotide polymorphism (SNP) encoding the R47H variant in murine Trem2. TREM2 expression, myeloid cell responses to amyloid deposition, plaque burden, and neuritic dystrophy were assessed at 4 months of age.

Results

AD mice heterozygous for the Trem2 R47H allele exhibi

SUBMITTER: Cheng-Hathaway PJ 

PROVIDER: S-EPMC5984804 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature