Title

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

Authors

Umber Dube
Jorge L. Del-Aguila
Zeran Li
John P. Budde
Shan Jiang
Simon Hsu
Laura Ibanez
Maria Victoria Fernandez
Fabiana Farias
Joanne Norton
Jen Gentsch
Fengxian Wang
Celeste M. Karch
Oscar Harari
Carlos Cruchaga
Randall J. Bateman
John C. Morris
Stephen Salloway
Colin L. Masters
Jae-Hong Lee
Neill R. Graff-Radford
Jasmeer P. Chhatwal
Ricardo Allegri
Patricio Chrem
Noelia Edigo
Fatima Amtashar
Tammie Benzinger
Susan Brandon
Virginia Buckles
Tamara Donahue
Anna Fagan
Angela Farrar
Gigi Flynn
Erin Franklin
Cortaiga Gant
Brian Gordon
Julia Gray
Jenny Gurney
Jason Hassenstab
David Holtzman
Russ Hornbeck
Gina Jerome
Daniel Marcus
Denise Maue-Dreyfus
Eric McDade
Joanne Norton
Richard Perrin
Marc Raichle
Wendy Sigurdson
Laura Swisher
Peter Wang
Mary Wolfsberger
Chengjie Xiong
Xiong Xu
Sarah Berman
Snezana Ikonomovic
William Klunk
Courtney Bodge
William Brooks
Mirelle D'Mello
Peter Schofield
Jill Buck
Marty Farlow
Bernardino Ghetti
Sochenda Chea
Jack Clifford
Nilufer Erekin-Taner
Helena Chui
Lucy Montoya
John Ringman
Jake Cinco
Jane Douglas
Nick Fox
Howard Feldman
Hisako Fujii
Hiroshi Mori
Hiroyuki Shimada
Samantha Gardener, Edith Cowan UniversityFollow
Ralph Martins, Edith Cowan UniversityFollow
Hamid Sohrabi, Edith Cowan UniversityFollow
Kevin Taddei, Edith Cowan UniversityFollow
Alison Goate
Jen Wang
Jill Goldman
Katie Neimeyer
James Noble
Mie Hirohara
Takeshi Kawarabayashi
Tomoyo Shiroto
Mikio Shoji
Siri Houeland DiBari
Johannes Levin
Takeshi Ikeuchi
Kensaku Kasuga
Mathias Jucker
Elke Kuder-Buletta
Christoph Laske
Robert Koeppe
Neal Scott Mason
Akem Nagamatsu
Kazushi Suzuki
Jee Hoon Roh
Paige Sparks
Mark Weiner
the Dominantly Inherited Alzheimer Network (DIAN)

Document Type

Journal Article

Publication Title

Nature Neuroscience

ISSN

1546-1726

PubMed ID

31591557

Publisher

Nature

School

School of Medical and Health Sciences

Funders

This work was supported by grants from the National Institutes of Health (NIH: grant nos R01AG044546, P01AG003991, RF1AG053303, R01AG058501, U01AG058922, RF1AG058501 and R01AG057777), the Alzheimer Association (grant nos NIRG-11-200110, BAND-14-338165, AARG-16-441560 and BFG-15-362540), grant no. NIH AG046374 (C.M.K.), Tau Consortium (C.M.K.) and grant no. K23 AG049087 (J.P.C.).

The recruitment and clinical characterization of research participants at Washington University were supported by NIH P50 AG05681, P01 AG03991, and P01 AG026276.

Data collection and sharing for this project were supported by DIAN (UF1AG032438) funded by the National Institute on Aging, the German Center for Neurodegenerative Diseases, Raul Carrea Institute for Neurological Research, with partial support by the Research and Development Grants for Dementia from the Japan Agency for Medical Research and Development, and the Korea Health Technology R&D Project through the Korea Health Industry Development Institute.

Comments

Originally published as: Dube, U., Del-Aguila, J. L., Li, Z., Budde, J. P., Jiang, S., Hsu, S., ... & Weiner, M. (2019). An atlas of cortical circular RNA expression in Alzheimer disease brains demonstrates clinical and pathological associations. Nature Neuroscience, 22, 1903-1912.

Original article available here.

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.

DOI

10.1038/s41593-019-0501-5

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