An atlas of cortical circular RNA expression in Alzheimer disease brains demonstrates clinical and pathological associations.

Abstract

Parietal cortex RNA-sequencing (RNA-seq) data were generated from individuals with and without Alzheimer disease (AD; ncontrol = 13; nAD = 83) from the Knight Alzheimer Disease Research Center (Knight ADRC). Using this and an independent (Mount Sinai Brain Bank (MSBB)) AD RNA-seq dataset, cortical circular RNA (circRNA) expression was quantified in the context of AD. Significant associations were identified between circRNA expression and AD diagnosis, clinical dementia severity and neuropathological severity. It was demonstrated that most circRNA-AD associations are independent of changes in cognate linear messenger RNA expression or estimated brain cell-type proportions. Evidence was provided for circRNA expression changes occurring early in presymptomatic AD and in autosomal dominant AD. It was also observed that AD-associated circRNAs co-expressed with known AD genes. Finally, potential microRNA-binding sites were identified in AD-associated circRNAs for miRNAs predicted to target AD genes. Together, these results highlight the importance of analyzing non-linear RNAs and support future studies exploring the potential roles of circRNAs in AD pathogenesis.

• Authors: Umber Dube, Jorge L Del-Aguila, Zeran Li, John P Budde, Shan Jiang, Simon Hsu, Laura Ibanez, Maria Victoria Fernandez, Fabiana Farias, Joanne Norton, Jen Gentsch, Fengxian Wang, Dominantly Inherited Alzheimer Network (DIAN), Stephen Salloway, Colin L Masters, Jae-Hong Lee, Neill R Graff-Radford, Jasmeer P Chhatwal, Randall J Bateman, John C Morris, Celeste M Karch, Oscar Harari, Carlos Cruchaga
• Journal: Nature neuroscience (Nat Neurosci) Vol. 22 Issue 11 Pg. 1903-1912 (11 2019) ISSN: 1546-1726 [Electronic] United States
• PMID: 31591557 (Publication Type: Journal Article, Meta-Analysis, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• MicroRNAs
• RNA, Circular
• RNA, Messenger

Topics

• Alzheimer Disease (diagnosis, metabolism, pathology)
• Atlases as Topic
• Case-Control Studies
• Gene Expression Profiling
• Humans
• MicroRNAs (metabolism)
• Parietal Lobe (metabolism)
• RNA, Circular (biosynthesis)
• RNA, Messenger (biosynthesis)
• Sequence Analysis, RNA
• Severity of Illness Index