期刊
NATURE NEUROSCIENCE
卷 22, 期 11, 页码 1903-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41593-019-0501-5
关键词
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资金
- National Institutes of Health (NIH) [R01AG044546, P01AG003991, RF1AG053303, R01AG058501, U01AG058922, RF1AG058501, R01AG057777]
- Alzheimer Association [NIRG-11-200110, BAND-14-338165, AARG-16-441560, BFG-15-362540]
- Tau Consortium
- NIH [P50 AG05681, P01 AG03991, P01 AG026276]
- DIAN - National Institute on Aging [UF1AG032438]
- German Center for Neurodegenerative Diseases
- Raul Carrea Institute for Neurological Research
- Research and Development Grants for Dementia from the Japan Agency for Medical Research and Development
- Korea Health Technology R&D Project through the Korea Health Industry Development Institute
- [NIH AG046374]
- [K23 AG049087]
Parietal cortex RNA-sequencing (RNA-seq) data were generated from individuals with and without Alzheimer disease (AD; n(control) = 13; n(AD) = 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 coexpressed 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.
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