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An atlas of cortical circular RNA expression in Alzheimer disease brains demonstrates clinical and pathological associations
Open accessAbstract
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 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.
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“A very recent study has established an association between circRNA expression and AD [620].”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [620]
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Background
Metadata
- Authors
- Dube, U., Del-Aguila, J. L., Li, Z., Budde, J. P., Jiang, S., Hsu, S., Ibanez, L., Fernandez, M. V., Farias, F., Norton, J., Gentsch, J., Wang, F., the Dominantly Inherited Alzheimer Network (DIAN), Allegri, R., Amtashar, F., Benzinger, T., Berman, S., Bodge, C., Brandon, S., Brooks, W., Buck, J., Buckles, V., Chea, S., Chrem, P., Chui, H., Cinco, J., Clifford, J., D’Mello, M., Donahue, T., Douglas, J., Edigo, N., Erekin-Taner, N., Fagan, A., Farlow, M., Farrar, A., Feldman, H., Flynn, G., Fox, N., Franklin, E., Fujii, H., Gant, C., Gardener, S., Ghetti, B., Goate, A., Goldman, J., Gordon, B., Gray, J., Gurney, J., Hassenstab, J., Hirohara, M., Holtzman, D., Hornbeck, R., DiBari, S. H., Ikeuchi, T., Ikonomovic, S., Jerome, G., Jucker, M., Kasuga, K., Kawarabayashi, T., Klunk, W., Koeppe, R., Kuder-Buletta, E., Laske, C., Levin, J., Marcus, D., Martins, R., Mason, N. S., Maue-Dreyfus, D., McDade, E., Montoya, L., Mori, H., Nagamatsu, A., Neimeyer, K., Noble, J., Norton, J., Perrin, R., Raichle, M., Ringman, J., Roh, J. H., Schofield, P., Shimada, H., Shiroto, T., Shoji, M., Sigurdson, W., Sohrabi, H., Sparks, P., Suzuki, K., Swisher, L., Taddei, K., Wang, J., Wang, P., Weiner, M., Wolfsberger, M., Xiong, C., Xu, X., Salloway, S., Masters, C. L., Lee, J.-H., Graff-Radford, N. R., Chhatwal, J. P., Bateman, R. J., Morris, J. C., Karch, C. M., Harari, O., & Cruchaga, C.
- Affiliations
- Washington University in St. Louis (US)
- Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia (AR)
- University of Pittsburgh (US)
- Indiana University Bloomington (US)
- Mayo Clinic (US)
- University of Southern California (US)
- Edith Cowan University (AU)
- Columbia University (US)
- Hirosaki University (JP)
- German Center for Neurodegenerative Diseases (DE)
- University of Michigan (US)
- Osaka City University (JP)
- The University of Tokyo (JP)
- Asan Medical Center (KR)
- Brigham and Women's Hospital (US)
- University of California, San Francisco (US)
- The University of Melbourne (AU)
- University of Ulsan (KR)
- Harvard University (US)
- Corresponding author
- Cruchaga, Carlos
- ORCID
- Dube, Umber
- Li, Zeran
- Budde, John P
- Jiang, Shan
- Hsu, Simon
- Wang, Fengxian
- Allegri, Ricardo
- Benzinger, Tammie
- Berman, Sarah
- Brooks, William
- D’Mello, Mirelle
- Fagan, Anne
- Feldman, Howard
- Fox, Nick
- Franklin, Erin
- Fujii, Hisako
- Gardener, Samantha
- Ghetti, Bernardino
- Goate, Alison
- Goldman, Jill
- Gordon, Brian
- Gurney, Jenny
- Hassenstab, Jason
- Holtzman, David
- Hornbeck, Russ
- Ikeuchi, Takeshi
- Jucker, Mathias
- Kasuga, Kensaku
- Kawarabayashi, Takeshi
- Klunk, William
- Laske, Christoph
- Levin, Johannes
- Martins, Ralph
- McDade, Eric
- Mori, Hiroshi
- Noble, James
- Perrin, Richard
- Ringman, John
- Roh, Jee Hoon
- Schofield, Peter
- Shoji, Mikio
- Sohrabi, Hamid
- Suzuki, Kazushi
- Taddei, Kevin
- Wang, Jen
- Xiong, Chengjie
- Salloway, Stephen
- Masters, Colin L
- Lee, Jae-Hong
- Chhatwal, Jasmeer P
- Bateman, Randall J
- Morris, John C
- Karch, Celeste M
- Harari, Oscar
- Cruchaga, Carlos
- Venue
- Nature Neuroscience
- Published
- 2019-10-07
- Volume
- 22
- Issue
- 11
- Pages
- 1903-1912
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC6858549
- OpenAlex
- W2977553419
- Cited by
- 345
- References
- 63
- Citations by year
- 2026: 22 · 2025: 43 · 2024: 45 · 2023: 53 · 2022: 69 · 2021: 60 · 2020: 48 · 2019: 3
- FWCI
- 14.89
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Murdoch University Research Portal (submittedVersion)
- UWA Profiles and Research Repository (UWA) (submittedVersion)
- Edith Cowan University Research Online (Edith Cowan University) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- DZNE Pub (submittedVersion)
- Funders
- U.S. Department of Health & Human Services | NIH | National Institute on Aging (RF1AG053303, R01AG058501, RF1AG058501)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Circular RNAs in diseases
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- circular RNA, Alzheimer's disease, parietal cortex, autosomal dominant Alzheimer's disease, microRNA binding sites, non-coding RNA, brain transcriptome
- MeSH terms
- RNA, Circular, Alzheimer Disease, Atlases as Topic, Humans, Parietal Lobe, RNA, Messenger, Severity of Illness Index, Case-Control Studies, Sequence Analysis, RNA, Gene Expression Profiling, MicroRNAs
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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