Comprehensive Characterization of the Transcriptional Landscape in Alzheimer’s Disease (AD) Brains

Authors

Chengxuan Chen
Zhao Zhang
Yuan Liu
Wei Hong
Hande Karahan
Jun Wang
Wenbo Li
Lixia Diao
Meichen Yu
Andrew J Saykin
Kwangsik Nho
Jungsu Kim
Leng Han

Publication Date

1-3-2025

Journal

Science Advances

Abstract

Alzheimer's disease (AD) is the leading dementia among the elderly with complex origins. Despite extensive investigation into the AD-associated protein-coding genes, the involvement of noncoding RNAs (ncRNAs) and posttranscriptional modification (PTM) in AD pathogenesis remains unclear. Here, we comprehensively characterized the landscape of ncRNAs and PTM events in 1460 samples across six brain regions sourced from the Mount Sinai/JJ Peters VA Medical Center Brain Bank Study and Mayo cohorts, encompassing 33,321 long ncRNAs, 92,897 enhancer RNAs, 53,763 alternative polyadenylation events, and 900,221 A-to-I RNA editing events. We additionally identified 25,351 aberrantly expressed ncRNAs and altered PTM events associated with AD traits and further identified the corresponding protein-coding genes to construct regulatory networks. Furthermore, we developed a user-friendly data portal, ADatlas, facilitating users in exploring our results. Our study aims to establish a comprehensive data platform for ncRNAs and PTMs in AD to advance related research.

Keywords

Alzheimer Disease, Humans, Brain, Gene Regulatory Networks, RNA, Untranslated, RNA, Long Noncoding, Gene Expression Profiling, Transcriptome, Transcription, Genetic, RNA Editing, Male, Gene Expression Regulation

DOI

10.1126/sciadv.adn1927

PMID

39752483

PMCID

PMC11698078

PubMedCentral® Posted Date

1-3-2025

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes