Single-nucleus multi-omics identifies shared and distinct pathways in Pick's and Alzheimer's disease.

ABSTRACT: The study of neurodegenerative diseases, particularly tauopathies like Pick's disease (PiD) and Alzheimer's disease (AD), offers insights into the underlying regulatory mechanisms. By investigating epigenomic variations in these conditions, we identified critical regulatory changes driving disease progression, revealing potential therapeutic targets. Our comparative analyses uncovered disease-enriched non-coding regions and genome-wide transcription factor (TF) binding differences, linking them to target genes. Notably, we identified a distal human-gained enhancer (HGE) associated with E3 ubiquitin ligase (UBE3A), highlighting disease-specific regulatory alterations. Additionally, fine-mapping of AD risk genes uncovered loci enriched in microglial enhancers and accessible in other cell typ

SUBMITTER: Shi Z 

PROVIDER: S-EPMC11398495 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature