In vivo validation of late-onset Alzheimer's disease genetic risk factors.

ABSTRACT:

Introduction

Genome-wide association studies have identified over 70 genetic loci associated with late-onset Alzheimer's disease (LOAD), but few candidate polymorphisms have been functionally assessed for disease relevance and mechanism of action.

Methods

Candidate genetic risk variants were informatically prioritized and individually engineered into a LOAD-sensitized mouse model that carries the AD risk variants APOE ε4/ε4 and Trem2*R47H. The potential disease relevance of each model was assessed by comparing brain transcriptomes measured with the Nanostring Mouse AD Panel at 4 and 12 months of age with human study cohorts.

Results

We created new models for 11 coding and loss-of-function risk variants. Transcriptomic effects from multiple genetic variants recapitulat

SUBMITTER: Sasner M 

PROVIDER: S-EPMC11247676 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature