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

被引：266

作者：

Dube, Umber ^{[1
,2
,3
]}

Del-Aguila, Jorge L. ^{[2
]}

Li, Zeran ^{[2
]}

Budde, John P. ^{[2
]}

Jiang, Shan ^{[2
]}

Hsu, Simon ^{[2
]}

Ibanez, Laura ^{[2
]}

Fernandez, Maria Victoria ^{[2
]}

Farias, Fabiana ^{[2
]}

Norton, Joanne ^{[2
]}

Gentsch, Jen ^{[2
]}

Wang, Fengxian ^{[2
]}

Salloway, Stephen ^{[4
]}

Masters, Colin L. ^{[5
]}

Lee, Jae-Hong ^{[6
]}

Graff-Radford, Neill R. ^{[7
]}

Chhatwal, Jasmeer P. ^{[8
]}

Bateman, Randall J. ^{[3
]}

Morris, John C. ^{[3
]}

Karch, Celeste M. ^{[2
,9
]}

Harari, Oscar ^{[2
]}

Cruchaga, Carlos ^{[2
,3
,9
,10
]}

Allegri, Ricardo ^{[11
]}

Amtashar, Fatima ^{[12
]}

Benzinger, Tammie ^{[12
]}

Berman, Sarah ^{[13
]}

Bodge, Courtney ^{[14
]}

Brandon, Susan ^{[12
]}

Brooks, William ^{[15
]}

Buck, Jill ^{[16
]}

Buckles, Virginia ^{[12
]}

Chea, Sochenda ^{[17
]}

Chrem, Patricio ^{[11
]}

Chui, Helena ^{[18
]}

Cinco, Jake ^{[19
]}

Clifford, Jack ^{[17
]}

D'Mello, Mirelle ^{[15
]}

Donahue, Tamara ^{[12
]}

Douglas, Jane ^{[19
]}

Edigo, Noelia ^{[11
]}

Erekin-Taner, Nilufer ^{[17
]}

Fagan, Anne ^{[12
]}

Farlow, Marty ^{[16
]}

Farrar, Angela ^{[12
]}

Feldman, Howard ^{[20
]}

Flynn, Gigi ^{[12
]}

Fox, Nick ^{[19
]}

Franklie, Erin ^{[12
]}

Fujii, Hisako ^{[21
]}

Gant, Cortaiga ^{[12
]}

机构：

[1] Washington Univ, Sch Med, Med Scientist Training Program, St Louis, MO USA

[2] Washington Univ, Sch Med, Dept Psychiat, 660 S Euclid Ave,CB8134, St Louis, MO 63110 USA

[3] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA

[4] Brown Univ, Alpert Med Sch, 345 Blackstone Blvd, Providence, RI 02912 USA

[5] Univ Melbourne, Florey Inst, Howard Florey Labs, Level 1, Parkville, Vic, Australia

[6] Univ Ulsan, Dept Neurol, Coll Med, Seoul, South Korea

[7] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA

[8] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02115 USA

[9] Washington Univ, Sch Med, Hope Ctr Neurol Disorders, St Louis, MO 63130 USA

[10] Washington Univ, Sch Med, NeuroGen & Informat, St Louis, MO 63130 USA

[11] FLENI, Inst Neurol Res, Buenos Aires, DF, Argentina

[12] Washington Univ, St Louis Sch Med, St Louis, MO 63110 USA

[13] Univ Pittsburgh, Pittsburgh, PA USA

[14] Brown Univ, Butler Hosp, Providence, RI 02912 USA

[15] Neurosci Res Australia, Sydney, NSW, Australia

[16] Indiana Univ, Bloomington, IN USA

[17] Mayo Clin Jacksonville, 4500 San Pablo Rd, Jacksonville, FL 32224 USA

[18] Univ Southern Calif, Los Angeles, CA USA

[19] UCL, London, England

[20] Univ Calif San Diego, San Diego, CA 92103 USA

[21] Osaka City Univ, Osaka, Japan

[22] Edith Cowan Univ, Perth, WA, Australia

[23] Icahn Sch Med Mt Sinai, New York, NY 10029 USA

[24] Columbia Univ, New York, NY USA

[25] Hirosaki Univ, Hirosaki, Aomori, Japan

[26] German Ctr Neurodegenerat Dis DZNE Munich, Munich, Germany

[27] Niigata Univ, Niigata, Japan

[28] German Ctr Neurodegnerat Dis DZNE Tubingen, Tubingen, Germany

[29] Univ Michigan, Ann Arbor, MI 48109 USA

[30] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA

[31] Univ Tokyo, Bunkyo Ku, Tokyo, Japan

[32] Asan Med Ctr, Seoul, South Korea

[33] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA

[34] Univ Calif San Francisco, San Francisco, CA 94143 USA

来源：

NATURE NEUROSCIENCE | 2019年 / 22卷 / 11期

基金：

美国国家卫生研究院;

关键词：

POSTERIOR CINGULATE; HYPOMETABOLISM; GENES; QUANTIFICATION; ATROPHY; ENERGY;

D O I：

10.1038/s41593-019-0501-5

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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.

引用

页码：1903 / +

页数：14

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