阿尔茨海默病（AD）大脑转录图谱的全面表征。

Comprehensive characterization of the transcriptional landscape in Alzheimer's disease (AD) brains.

作者信息

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

机构信息

Department of Biostatistics and Health Data Science, School of Medicine, Indiana University, Indianapolis, IN 46202, USA.

Brown Center for Immunotherapy, School of Medicine, Indiana University, Indianapolis, IN 46202, USA.

出版信息

Sci Adv. 2025 Jan 3;11(1):eadn1927. doi: 10.1126/sciadv.adn1927.

DOI:10.1126/sciadv.adn1927

PMID:39752483

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11698078/

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.

摘要

阿尔茨海默病（AD）是老年人中最主要的痴呆症，其发病机制复杂。尽管对与AD相关的蛋白质编码基因进行了广泛研究，但非编码RNA（ncRNAs）和转录后修饰（PTM）在AD发病机制中的作用仍不清楚。在此，我们全面表征了来自西奈山/JJ彼得斯退伍军人事务医疗中心脑库研究和梅奥队列的六个脑区1460个样本中的ncRNAs和PTM事件格局，包括33321个长链ncRNAs、92897个增强子RNA、53763个可变聚腺苷酸化事件和900221个A到I RNA编辑事件。我们还鉴定出25351个异常表达的ncRNAs和与AD特征相关的改变的PTM事件，并进一步鉴定出相应的蛋白质编码基因以构建调控网络。此外，我们开发了一个用户友好的数据门户ADatlas，方便用户探索我们的研究结果。我们的研究旨在建立一个关于AD中ncRNAs和PTMs的综合数据平台，以推动相关研究。