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

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

doi:10.1126/sciadv.adn1927

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

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

Authors

Chengxuan Chen^{1

2

3

4}, Zhao Zhang⁵, Yuan Liu^{1

2

3

4}, Wei Hong⁵, Hande Karahan^{6

7}, Jun Wang^{8

9}, Wenbo Li^{5

9}, Lixia Diao¹⁰, Meichen Yu^{11

12

13}, Andrew J Saykin^{11

12

13}, Kwangsik Nho^{3

11

12}, Jungsu Kim^{6

7}, Leng Han^{1

2

3

4

11}

Affiliations

¹ Department of Biostatistics and Health Data Science, School of Medicine, Indiana University, Indianapolis, IN 46202, USA.
² Brown Center for Immunotherapy, School of Medicine, Indiana University, Indianapolis, IN 46202, USA.
³ Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
⁴ Center for Epigenetics and Disease Prevention, Institute of Biosciences and Technology, Texas A&M University, Houston, TX 77030, USA.
⁵ Department of Biochemistry and Molecular Biology, McGovern Medical School, University of Texas Health Science Center, Houston, TX 77030, USA.
⁶ Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
⁷ Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
⁸ Department of Pediatrics, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
⁹ The University of Texas MD Anderson Cancer Center and UTHealth Graduate School of Biomedical Sciences, Houston, TX 77030, USA.
¹⁰ Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
¹¹ Indiana Alzheimer's Disease Research Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
¹² Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
¹³ Indiana University Network Science Institute, Bloomington, IN, USA.

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.

MeSH terms

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

Substances

RNA, Untranslated
RNA, Long Noncoding