Journal article

The effect of increased genetic risk for Alzheimer's disease on hippocampal and amygdala volume

Michelle K Lupton, Lachlan Strike, Narelle K Hansell, Wei Wen, Karen A Mather, Nicola J Armstrong, Anbupalam Thalamuthu, Katie L McMahon, Greig I de Zubicaray, Amelia A Assareh, Andrew Simmons, Petroula Proitsi, John F Powell, Grant W Montgomery, Derrek P Hibar, Eric Westman, Magda Tsolaki, Iwona Kloszewska, Hilkka Soininen, Patrizia Mecocci Show all



Reduction in hippocampal and amygdala volume measured via structural magnetic resonance imaging is an early marker of Alzheimer's disease (AD). Whether genetic risk factors for AD exert an effect on these subcortical structures independent of clinical status has not been fully investigated. We examine whether increased genetic risk for AD influences hippocampal and amygdala volumes in case-control and population cohorts at different ages, in 1674 older (aged >53 years; 17% AD, 39% mild cognitive impairment [MCI]) and 467 young (16-30 years) adults. An AD polygenic risk score combining common risk variants excluding apolipoprotein E (APOE), and a single nucleotide polymorphism in TREM2, were ..

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University of Melbourne Researchers


Awarded by Australian National Health and Medical Research Council (NHMRC)

Awarded by NHMRC/Australian Research Council Strategic Award

Awarded by NHMRC

Awarded by National Institute of Child Health and Human Development

Awarded by National Health and Medical Research Council, Australia

Awarded by European Union

Awarded by Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health)

Awarded by DOD ADNI (Department of Defense)

Awarded by Medical Research Council

Awarded by Alzheimer's Research UK

Awarded by Wellcome Trust

Awarded by German Federal Ministry of Education and Research (BMBF): Competence Network Dementia (CND)

Awarded by NIH/NIA

Awarded by NIA

Awarded by AGES

Awarded by NHLBI

Awarded by Alzheimer's Association

Awarded by 7FP grant

Awarded by NIH Big Data Center of Excellence

Awarded by Alzheimer's Society

Funding Acknowledgements

[ "The authors would like to acknowledge and thank the Sydney MAS and OATS participants, their supporters, and their research teams. Sydney MAS is supported by the Program Grants 350833 and 568969 from the Australian National Health and Medical Research Council (NHMRC). The NHMRC/Australian Research Council Strategic Award 401162 and NHMRC Project Grant 1045325 support OATS, which was facilitated through access to the Australian Twin Registry (ATR). The ATR is supported by the NHMRC Enabling Grant 310667, administered by the University of Melbourne. DNA was extracted by Genetic Repositories Australia, which was supported by the NHMRC Enabling Grant 401184. OATS genotyping was partly funded by a Commonwealth Scientific and Industrial Research Organisation Flagship Collaboration Fund Grant.", "For QTIM, they thank the twins for their participation, Kori Johnson and the radiographers for MRI scanning and preprocessing the images, Marlene Grace and Ann Eldridge for twin recruitment, Daniel Park for database support, Anjali Henders for DNA processing and preparation, Scott Gordon for quality control and management of the genotypes. The QTIM study was supported by the National Institute of Child Health and Human Development (R01 HD050735), and the National Health and Medical Research Council (NHMRC 486682, 1009064), Australia. Genotyping was supported by NHMRC (389875).", "AddNeuroMed is part of InnoMed (Innovative Medicines in Europe), an integrated project funded by the European Union of the Sixth Framework program priority ((FP6-2004-LIFESCIHEALTH-5); the Alzheimer's Research Trust UK; the John and Lucille van Geest Foundation; and the NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at the South London, Maudsley NHS Foundation Trust and Kings College London, and a joint infrastructure grant from Guy's and St Thomas' Charity and the Maudsley Charity; Academy of Finland, Kuopio University Hospital (HS) and funding from UEF-BRAIN (HS).", "Data collection and sharing for ADNI was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc; Biogen Idec; Bristol-Myers Squibb Company; Eisai; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC; Johnson & Johnson Pharmaceutical Research & Development LLC; Medpace; Merck & Co., Inc; Meso Scale Diagnostics, LLC; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc; Piramal Imaging; Servier; Synarc; and Takeda Pharmaceutical Company. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health ( The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California.", "The authors thank the International Genomics of Alzheimer's Project (IGAP) for providing summary results data for these analyses. The investigators within IGAP contributed to the design and implementation of IGAP and/or provided data but did not participate in analysis or writing of this report. IGAP was made possible by the generous participation of the control subjects, the patients, and their families. The i-Select chips were funded by the French National Foundation on Alzheimer's disease and related disorders. EADI was supported by the LABEX (laboratory of excellence program investment for the future) DISTALZ grant, Inserm, Institut Pasteur de Lille, Universite de Lille 2 and the Lille University Hospital. GERAD was supported by the Medical Research Council (Grant no 503480), Alzheimer's Research UK (Grant no 503176), the Wellcome Trust (Grant no 082604/2/07/Z), and German Federal Ministry of Education and Research (BMBF): Competence Network Dementia (CND) grant no 01GI0102, 01GI0711, 01GI0420. CHARGE was partly supported by the NIH/NIA grant R01 AG033193 and the NIA AG081220 and AGES contract N01-AG-12100, the NHLBI grant R01 HL105756, the Icelandic Heart Association, and the Erasmus Medical Centre and Erasmus University. ADGC was supported by the NIH/NIA grants: U01 AG032984, U24 AG021886, U01 AG016976, and the Alzheimer's Association grant ADGC-10-196728.", "Michelle Lupton is supported by a Perpetual Foundation Wilson Fellowship for early career researchers. Hilkka Soininen has received funding from 7FP grant agreement no 601055 VPH-DARE@IT. Karen Mather is supported by an Alzheimer's Australia Dementia Research Foundation Postdoctoral Fellowship and the NHMRC Capacity Building Grant 568940. Paul Thompson and Derrek Hibar are supported, in part, by an NIH Big Data Center of Excellence Grant (U54 EB020403), funded by multiple NIH institutes, including NIBIB and NCI." ]