Widespread transposable element dysregulation in human aging brains with Alzheimer's disease.

ABSTRACT:

Introduction

Transposable element (TE) dysregulation is associated with neuroinflammation in Alzheimer's disease (AD) brains. Yet, TE quantitative trait loci (teQTL) have not been well characterized in human aged brains with AD.

Methods

We leveraged large-scale bulk and single-cell RNA sequencing, whole-genome sequencing (WGS), and xQTL from three human AD brain biobanks to characterize TE expression dysregulation and experimentally validate AD-associated TEs using CRISPR interference (CRISPRi) assays in human induced pluripotent stem cell (iPSC)-derived neurons.

Results

We identified 26,188 genome-wide significant TE expression QTLs (teQTLs) in human aged brains. Subsequent colocalization analysis of teQTLs with AD genetic loci identified AD-associated teQTLs and lin

SUBMITTER: Feng Y 

PROVIDER: S-EPMC11567813 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature