Targeted neurogenesis pathway-based gene analysis identifies ADORA2 Aassociated with hippocampal volume in mild cognitive impairment and Alzheimer's disease

NEUROBIOLOGY OF AGING

卷:60

Article

Horgusluoglu-Moloch, Emrin^1,2  Nho, Kwangsik^2,3,4  Risacher, Shannon L.^2,4  Kim, Sungeun^2,5  Foroud, Tatiana^1,3,4  Shaw, Leslie M.⁶  Trojanowski, John Q.⁶  Aisen, Paul S.⁷  Petersen, Ronald C.⁸  Jack, Clifford R., Jr.⁹  Lovestone, Simon¹⁰  Simmons, Andrew¹⁰  Weiner, Michael W.^11,12,13,14  Saykin, Andrew J.^1,2,3,4 

[1] Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA

[2] Indiana Univ Sch Med, Dept Radiol & Imaging Sci, Ctr Neuroimaging, Indianapolis, IN 46202 USA

[3] Indiana Univ Sch Med, Ctr Computat Biol & Bioinformat, Indianapolis, IN 46202 USA

[4] Indiana Univ Sch Med, Indiana Alzheimer Dis Ctr, Indianapolis, IN 46202 USA

[5] SUNY Coll Oswego, Dept Elect & Comp Engn, Oswego, NY USA

[6] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA

[7] Univ Southern Calif, Dept Neurol, San Diego, CA USA

[8] Mayo Clin Minnesota, Dept Neurol, Rochester, MN USA

[9] Mayo Clin Minnesota, Dept Radiol, Rochester, MN USA

[10] Kings Coll London, Inst Psychiat, London, England

[11] Univ Calif San Francisco, Dept Radiol, San Francisco, CA USA

[12] Univ Calif San Francisco, Dept Med, San Francisco, CA USA

[13] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA

[14] Dept Vet Affairs Med Ctr, San Francisco, CA USA

关键词: Neurogenesis;    ADORA2A;    Hippocampal volume;    Memory;    Alzheimer's disease;    Gene-based association analysis;    NMDA-receptor antagonist;   

DOI  :  10.1016/j.neurobiolaging.2017.08.010

来源: Elsevier

【 摘 要 】

Alzheimer's disease (AD) patients display hippocampal atrophy, memory impairment, and cognitive decline. New neurons are generated throughout adulthood in 2 regions of the brain implicated in AD, the dentate gyrus of the hippocampus and the subventricular zone of the olfactory bulb. Disruption of this process contributes to neurodegenerative diseases including AD, and many of the molecular players in AD are also modulators of adult neurogenesis. However, the genetic mechanisms underlying adult neurogenesis in AD have been underexplored. To address this gap, we performed a gene-based association analysis in cognitively normal and impaired participants using neurogenesis pathway-related candidate genes curated from existing databases, literature mining, and large-scale genome-wide association study findings. A gene-based association analysis identified adenosine A2a receptor (ADORA2A) as significantly associated with hippocampal volume and the association between rs9608282 within ADORA2A and hippocampal volume was replicated in the meta-analysis after multiple comparison adjustments (p = 7.88 x 10(-6)). The minor allele of rs9608282 in ADORA2A is associated with larger hippocampal volumes and better memory. (C) 2017 Elsevier Inc. All rights reserved.

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