Lower expression of <i>BIN1's</i> neuronal isoform in vulnerable excitatory neurons increases risk in Alzheimer's disease.

ABSTRACT:

Background

Neurons in Alzheimer's disease (AD) experience elevated DNA damage, with DNA repair sites enriched at enhancer regions of genes essential for neuronal survival. Excitatory neurons in the cortical superficial layers expressing CUX2 and RORB (Cux2+/Rorb+), are selectively vulnerable in AD, but their relationship to single nucleotide polymorphisms (SNPs) in AD genome-wide association studies (GWAS) is unclear.

Objective

This study aimed to identify and characterize functional AD-GWAS SNPs using single-nucleus RNA sequencing data, focusing on selectively vulnerable neurons and DNA repair hotspots.

Methods

Filters were applied to identify candidate SNPs based on overlap with repair hotspots, RNA expression, transcription factor binding, AD associat

SUBMITTER: Ranganathan R 

PROVIDER: S-EPMC11864243 | biostudies-literature | 2025 Jan-Dec

REPOSITORIES: biostudies-literature