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Genetic Analysis of Association Between Calcium Signaling and Hippocampal Activation, Memory Performance in the Young and Old, and Risk for Sporadic Alzheimer Disease

Heck, Angela and Fastenrath, Matthias and Coynel, David and Auschra, Bianca and Bickel, Horst and Freytag, Virginie and Gschwind, Leo and Hartmann, Francina and Jessen, Frank and Kaduszkiewicz, Hanna and Maier, Wolfgang and Milnik, Annette and Pentzek, Michael and Riedel-Heller, Steffi G. and Spalek, Klara and Vogler, Christian and Wagner, Michael and Weyerer, Siegfried and Wolfsgruber, Steffen and de Quervain, Dominique J.-F. and Papassotiropoulos, Andreas. (2015) Genetic Analysis of Association Between Calcium Signaling and Hippocampal Activation, Memory Performance in the Young and Old, and Risk for Sporadic Alzheimer Disease. JAMA Psychiatry, 72 (10). pp. 1029-1036.

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Official URL: http://edoc.unibas.ch/40818/

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Abstract

Human episodic memory performance is linked to the function of specific brain regions, including the hippocampus; declines as a result of increasing age; and is markedly disturbed in Alzheimer disease (AD), an age-associated neurodegenerative disorder that primarily affects the hippocampus. Exploring the molecular underpinnings of human episodic memory is key to the understanding of hippocampus-dependent cognitive physiology and pathophysiology.; To determine whether biologically defined groups of genes are enriched in episodic memory performance across age, memory encoding-related brain activity, and AD.; In this multicenter collaborative study, which began in August 2008 and is ongoing, gene set enrichment analysis was done by using primary and meta-analysis data from 57 968 participants. The Swiss cohorts consisted of 3043 healthy young adults assessed for episodic memory performance. In a subgroup (n = 1119) of one of these cohorts, functional magnetic resonance imaging was used to identify gene set-dependent differences in brain activity related to episodic memory. The German Study on Aging, Cognition, and Dementia in Primary Care Patients cohort consisted of 763 elderly participants without dementia who were assessed for episodic memory performance. The International Genomics of Alzheimer's Project case-control sample consisted of 54 162 participants (17 008 patients with sporadic AD and 37 154 control participants). Analyses were conducted between January 2014 and June 2015. Gene set enrichment analysis in all samples was done using genome-wide single-nucleotide polymorphism data.; Episodic memory performance in the Swiss cohort and German Study on Aging, Cognition, and Dementia in Primary Care Patients cohort was quantified by picture and verbal delayed free recall tasks. In the functional magnetic resonance imaging experiment, activation of the hippocampus during encoding of pictures served as the phenotype of interest. In the International Genomics of Alzheimer's Project sample, diagnosis of sporadic AD served as the phenotype of interest.; In the discovery sample, we detected significant enrichment for genes constituting the calcium signaling pathway, especially those related to the elevation of cytosolic calcium (P = 2 × 10-4). This enrichment was replicated in 2 additional samples of healthy young individuals (P = .02 and .04, respectively) and a sample of healthy elderly participants (P = .004). Hippocampal activation (P = 4 × 10-4) and the risk for sporadic AD (P = .01) were also significantly enriched for genes related to the elevation of cytosolic calcium.; By detecting consistent significant enrichment in independent cohorts of young and elderly participants, this study identified that calcium signaling plays a central role in hippocampus-dependent human memory processes in cognitive health and disease, contributing to the understanding and potential treatment of hippocampus-dependent cognitive pathology.
Faculties and Departments:03 Faculty of Medicine > Bereich Psychiatrie (Klinik) > Erwachsenenpsychiatrie UPK > Kognitive Neurowissenschaften (de Quervain)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Psychiatrie (Klinik) > Erwachsenenpsychiatrie UPK > Kognitive Neurowissenschaften (de Quervain)
03 Faculty of Medicine > Bereich Psychiatrie (Klinik) > Erwachsenenpsychiatrie UPK > Molekulare Neurowissenschaften (Papassotiropoulos)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Psychiatrie (Klinik) > Erwachsenenpsychiatrie UPK > Molekulare Neurowissenschaften (Papassotiropoulos)
05 Faculty of Science > Departement Biozentrum > Services Biozentrum > Life Sciences Training Facility (Papassotiropoulos)
07 Faculty of Psychology
07 Faculty of Psychology > Departement Psychologie > Forschungsbereich Klinische Psychologie und Neurowissenschaften > Cognitive Neuroscience (de Quervain)
07 Faculty of Psychology > Departement Psychologie > Forschungsbereich Klinische Psychologie und Neurowissenschaften > Molecular Psychology (Papassotiropoulos)
UniBasel Contributors:Milnik, Annette and Heck, Angela and Fastenrath, Matthias and Coynel, David and Auschra, Bianca and Freytag, Virginie and Gschwind, Leo and Vogler, Christian and de Quervain, Dominique J.-F. and Papassotiropoulos, Andreas
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Medical Association
ISSN:2168-6238
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:10 Jan 2019 14:53
Deposited On:26 Jan 2016 08:00

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