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

2019; Nature Portfolio; Volume: 22; Issue: 11 Linguagem: Inglês

10.1038/s41593-019-0501-5

1546-1726

Umber Dube, Jorge L. Del-Águila, Zeran Li, John Budde, Shan Jiang, Simon Hsu, Laura Ibáñez, María Victoria Fernández, Fabiana H.G. Farias, Joanne Norton, Jen Gentsch, Fengxian Wang, Ricardo Allegri, Fatima Amtashar, Tammie L.S. Benzinger, Sarah Berman, Courtney Bodge, Susan Brandon, William S. Brooks, Jill Buck, Virginia Buckles, Sochenda Chea, Patricio Chrem, Helena Chui, Jake Cinco, Clifford Jack, Mirelle D’Mello, Tamara Donahue, J G Douglas, Noelia Edigo, Nilufer Erekin-Taner, Anne M. Fagan, Marty Farlow, Angela Farrar, Howard Feldman, Gigi Flynn, Nick C. Fox, Erin Franklin, Hisako Fujii, Cortaiga Gant, Samantha L. Gardener, Bernardino Ghetti, Alison Goate, Jill Goldman, Brian A. Gordon, Julia Gray, Jenny Gurney, Jason Hassenstab, Mie Hirohara, David M. Holtzman, Russ C. Hornbeck, Siri Houeland DiBari, Takeshi Ikeuchi, Snežana Ikonomović, Gina Jerome, Mathias Jucker, Kensaku Kasuga, Takeshi Kawarabayashi, William E. Klunk, Robert Koeppe, Elke Kuder-Buletta, Christoph Laske, Johannes Levin, Daniel Marcus, Ralph N. Martins, Neal Scott Mason, Denise Maue-Dreyfus, Eric McDade, Lucy Montoya, Hiroshi Mori, Akem Nagamatsu, Katie Neimeyer, James M. Noble, Joanne Norton, Richard J. Perrin, Marc Raichle, John M. Ringman, Jee Hoon Roh, Peter R. Schofield, Hiroyuki Shimada, Tomoyo Shiroto, Mikio Shoji, Wendy Sigurdson, Hamid R. Sohrabi, Paige Sparks, Kazushi Suzuki, Laura Swisher, Kevin Taddei, Jen Wang, Peter Wang, Mike Weiner, Mary Wolfsberger, Chengjie Xiong, Xu Xiong, 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,

RNA Research and Splicing

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.