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Nat Neurosci. 2019 Nov;22(11):1903-1912. doi: 10.1038/s41593-019-0501-5. Epub 2019 Oct 7.

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

Author information

1
Medical Scientist Training Program, Washington University School of Medicine, St. Louis, MO, USA.
2
Department of Psychiatry, Washington University School of Medicine, 660 S. Euclid Ave. CB8134, St. Louis, MO, USA.
3
Department of Neurology, Washington University School of Medicine, St Louis, MO, USA.
4
Alpert Medical School of Brown University, 345 Blackstone Boulevard, Providence, RI, USA.
5
The Florey Institute, the University of Melbourne. Level 1, Howard Florey Laboratories, Royal Parade, Parkville, VIC, Australia.
6
Department of Neurology, University of Ulsan College of Medicine, Seoul, Korea.
7
Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
8
Massachusetts General Hospital, Department of Neurology, Harvard Medical School, Boston, MA, USA.
9
Hope Center for Neurological Disorders. Washington University School of Medicine, St. Louis, MO, USA.
10
Department of Psychiatry, Washington University School of Medicine, 660 S. Euclid Ave. CB8134, St. Louis, MO, USA. ccruchaga@wustl.edu.
11
Department of Neurology, Washington University School of Medicine, St Louis, MO, USA. ccruchaga@wustl.edu.
12
Hope Center for Neurological Disorders. Washington University School of Medicine, St. Louis, MO, USA. ccruchaga@wustl.edu.
13
NeuroGenomics and Informatics, Washington University School of Medicine, St. Louis, MO, USA. ccruchaga@wustl.edu.

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.

PMID:
31591557
PMCID:
PMC6858549
[Available on 2020-04-07]
DOI:
10.1038/s41593-019-0501-5

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