Neurobiol Aging. 2016 Apr;40:68-77. doi: 10.1016/j.neurobiolaging.2015.12.023. Epub 2016 Jan 11.

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

Lupton MK¹, Strike L², Hansell NK², Wen W³, Mather KA³, Armstrong NJ⁴, Thalamuthu A³, McMahon KL⁵, de Zubicaray GI⁶, Assareh AA³, Simmons A⁷, Proitsi P⁷, Powell JF⁷, Montgomery GW⁸, Hibar DP⁹, Westman E¹⁰, Tsolaki M¹¹, Kloszewska I¹², Soininen H¹³, Mecocci P¹⁴, Velas B¹⁵, Lovestone S¹⁶; Alzheimer's Disease Neuroimaging Initiative, Brodaty H³, Ames D¹⁷, Trollor JN³, Martin NG⁸, Thompson PM⁹, Sachdev PS³, Wright MJ¹⁸.

Author information

1: Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. Electronic address: Michelle.Lupton@qimrberghofer.edu.au.
2: Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia; Queensland Brain Institute, The University of Queensland, St Lucia, Queensland, Australia.
3: Centre for Healthy Brain Ageing, University of New South Wales, Sydney, New South Wales, Australia.
4: Mathematics and Statistics, Murdoch University, Perth, Western Australia, Australia.
5: Centre for Advanced Imaging, University of Queensland, Brisbane, Queensland, Australia.
6: Faculty of Health and Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Brisbane, Queensland, Australia.
7: Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
8: Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
9: Imaging Genetics Center, Keck School of Medicine, University of Southern California, Marina del Ray, CA, USA.
10: Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Alzheimer's Disease Research Centre, Karolinska Institute, Stockholm, Sweden.
11: Memory and Dementia Centre, Aristotle University of Thessaloniki, Thessaloniki, Greece.
12: Department of Old Age Psychiatry & Psychotic Disorders, Medical University of Lodz, Lodz, Poland.
13: Department of Neurology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
14: Section of Gerontology and Geriatrics, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy.
15: Gerontopole, CHU, UMR INSERM 1027, University of Toulouse, France.
16: Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK; Department of Psychiatry, Warneford Hospital, University of Oxford, Oxford, UK.
17: National Ageing Research Institute, Parkville, Victoria, Australia; Academic Unit for Psychiatry of Old Age, University of Melbourne, Kew, Victoria, Australia.
18: Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia; Queensland Brain Institute, The University of Queensland, St Lucia, Queensland, Australia; The Centre for Advanced Imaging, The University of Queensland, St Lucia, Queensland, Australia.

Abstract

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 both associated with reduced hippocampal volume in healthy older adults and those with MCI. APOE ε4 was associated with hippocampal and amygdala volume in those with AD and MCI but was not associated in healthy older adults. No associations were found in young adults. Genetic risk for AD affects the hippocampus before the clinical symptoms of AD, reflecting a neurodegenerative effect before clinical manifestations in older adults.