1. An atlas of cortical circular RNA expression in Alzheimer disease brains demonstrates clinical and pathological associations
- Author
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Dube, Umber, Del-Aguila, Jorge L, Gentsch, Jen, Wang, Peter, Weiner, Mike, Wolfsberger, Mary, Xiong, Chengjie, Xu, Xiong, Wang, Fengxian, Network, Dominantly Inherited Alzheimer, Salloway, Stephen, Masters, Colin L, Lee, Jae-Hong, Graff-Radford, Neill R, Chhatwal, Jasmeer P, Bateman, Randall J, Morris, John C, Li, Zeran, Karch, Celeste M, Harari, Oscar, Cruchaga, Carlos, Allegri, Ricardo, Amtashar, Fatima, Benzinger, Tammie, Berman, Sarah, Bodge, Courtney, Brandon, Susan, Brooks, William, Budde, John P, Buck, Jill, Buckles, Virginia, Chea, Sochenda, Chrem, Patricio, Chui, Helena, Cinco, Jake, Clifford, Jack, D'Mello, Mirelle, Donahue, Tamara, Douglas, Jane, Jiang, Shan, Edigo, Noelia, Erekin-Taner, Nilufer, Fagan, Anne, Farlow, Marty, Farrar, Angela, Feldman, Howard, Flynn, Gigi, Fox, Nick, Franklin, Erin, Fujii, Hisako, Hsu, Simon, Gant, Cortaiga, Gardener, Samantha, Ghetti, Bernardino, Goate, Alison, Goldman, Jill, Gordon, Brian, Gray, Julia, Gurney, Jenny, Hassenstab, Jason, Hirohara, Mie, Ibanez, Laura, Holtzman, David, Hornbeck, Russ, DiBari, Siri Houeland, Ikeuchi, Takeshi, Ikonomovic, Snezana, Jerome, Gina, Jucker, Mathias, Kasuga, Kensaku, Kawarabayashi, Takeshi, Klunk, William, Fernandez, Maria Victoria, Koeppe, Robert, Kuder-Buletta, Elke, Laske, Christoph, Levin, Johannes, Marcus, Daniel, Martins, Ralph, Mason, Neal Scott, Maue-Dreyfus, Denise, McDade, Eric, Montoya, Lucy, Farias, Fabiana, Mori, Hiroshi, Nagamatsu, Akem, Neimeyer, Katie, Noble, James, Norton, Joanne, Perrin, Richard, Raichle, Marc, Ringman, John, Roh, Jee Hoon, Schofield, Peter, Shimada, Hiroyuki, Shiroto, Tomoyo, Shoji, Mikio, Sigurdson, Wendy, Sohrabi, Hamid, Sparks, Paige, Suzuki, Kazushi, Swisher, Laura, Taddei, Kevin, and Wang, Jen
- Subjects
0301 basic medicine ,metabolism [Parietal Lobe] ,Posterior parietal cortex ,Biology ,Severity of Illness Index ,Article ,Pathogenesis ,03 medical and health sciences ,pathology [Alzheimer Disease] ,0302 clinical medicine ,Atlases as Topic ,Alzheimer Disease ,Circular RNA ,metabolism [MicroRNAs] ,Parietal Lobe ,ddc:570 ,microRNA ,medicine ,Dementia ,Humans ,RNA, Messenger ,Gene ,Messenger RNA ,biosynthesis [RNA, Messenger] ,Sequence Analysis, RNA ,General Neuroscience ,Gene Expression Profiling ,diagnosis [Alzheimer Disease] ,RNA, Circular ,medicine.disease ,biosynthesis [RNA, Circular] ,MicroRNAs ,030104 developmental biology ,Case-Control Studies ,Alzheimer's disease ,Neuroscience ,030217 neurology & neurosurgery ,metabolism [Alzheimer Disease] - 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.
- Published
- 2019