The TREM2 H157Y variant is associated with more severe neurodegeneration in Alzheimer's disease and altered immune-related processes.

ABSTRACT:

Introduction

Multiple TREM2 variants are associated with an increased risk of Alzheimer's disease (AD). TREM2 H157Y is the only variant located at the proteolytic cleavage site that enhances TREM2 protein shedding. While this variant is associated with increased AD risk predominantly in the Chinese population, its impact on AD pathology is largely unknown.

Methods

We conducted an in-depth study integrating clinical cases, neuroimaging data, and blood proteomic data.

Results

TREM2 H157Y variant carriers with AD exhibit more severe AD pathology, more severe neurodegeneration, and more rapid clinical progression. Cognitively normal individuals carrying the variant show changes in blood proteins that are associated with neurodegeneration and inflammation. Moreover, the TR

SUBMITTER: Tsui JSM 

PROVIDER: S-EPMC12441928 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature