title: The effect of increased genetic risk for Alzheimer's disease on hippocampal and amygdala volume.
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.
authors.affiliation: Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. Electronic address: Michelle.Lupton@qimrberghofer.edu.au.
authors.forename: Michelle K
authors.initials: MK
authors.lastname: Lupton
authors.affiliation: Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia; Queensland Brain Institute, The University of Queensland, St Lucia, Queensland, Australia.
authors.forename: Lachlan
authors.initials: L
authors.lastname: Strike
authors.affiliation: Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia; Queensland Brain Institute, The University of Queensland, St Lucia, Queensland, Australia.
authors.forename: Narelle K
authors.initials: NK
authors.lastname: Hansell
authors.affiliation: Centre for Healthy Brain Ageing, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Wei
authors.initials: W
authors.lastname: Wen
authors.affiliation: Centre for Healthy Brain Ageing, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Karen A
authors.initials: KA
authors.lastname: Mather
authors.affiliation: Mathematics and Statistics, Murdoch University, Perth, Western Australia, Australia.
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Armstrong
authors.affiliation: Centre for Healthy Brain Ageing, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Anbupalam
authors.initials: A
authors.lastname: Thalamuthu
authors.affiliation: Centre for Advanced Imaging, University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Katie L
authors.initials: KL
authors.lastname: McMahon
authors.affiliation: Faculty of Health and Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Brisbane, Queensland, Australia.
authors.forename: Greig I
authors.initials: GI
authors.lastname: de Zubicaray
authors.affiliation: Centre for Healthy Brain Ageing, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Amelia A
authors.initials: AA
authors.lastname: Assareh
authors.affiliation: Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Simmons
authors.affiliation: Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
authors.forename: Petroula
authors.initials: P
authors.lastname: Proitsi
authors.affiliation: Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
authors.forename: John F
authors.initials: JF
authors.lastname: Powell
authors.affiliation: Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
authors.forename: Grant W
authors.initials: GW
authors.lastname: Montgomery
authors.affiliation: Imaging Genetics Center, Keck School of Medicine, University of Southern California, Marina del Ray, CA, USA.
authors.forename: Derrek P
authors.initials: DP
authors.lastname: Hibar
authors.affiliation: Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Alzheimer's Disease Research Centre, Karolinska Institute, Stockholm, Sweden.
authors.forename: Eric
authors.initials: E
authors.lastname: Westman
authors.affiliation: Memory and Dementia Centre, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Magda
authors.initials: M
authors.lastname: Tsolaki
authors.affiliation: Department of Old Age Psychiatry & Psychotic Disorders, Medical University of Lodz, Lodz, Poland.
authors.forename: Iwona
authors.initials: I
authors.lastname: Kloszewska
authors.affiliation: Department of Neurology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
authors.forename: Hilkka
authors.initials: H
authors.lastname: Soininen
authors.affiliation: Section of Gerontology and Geriatrics, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Mecocci
authors.affiliation: Gerontopole, CHU, UMR INSERM 1027, University of Toulouse, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Velas
authors.affiliation: Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK; Department of Psychiatry, Warneford Hospital, University of Oxford, Oxford, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Lovestone
authors.affiliation: Centre for Healthy Brain Ageing, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Henry
authors.initials: H
authors.lastname: Brodaty
authors.affiliation: National Ageing Research Institute, Parkville, Victoria, Australia; Academic Unit for Psychiatry of Old Age, University of Melbourne, Kew, Victoria, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Ames
authors.affiliation: Centre for Healthy Brain Ageing, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Julian N
authors.initials: JN
authors.lastname: Trollor
authors.affiliation: Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Martin
authors.affiliation: Imaging Genetics Center, Keck School of Medicine, University of Southern California, Marina del Ray, CA, USA.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Thompson
authors.affiliation: Centre for Healthy Brain Ageing, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Perminder S
authors.initials: PS
authors.lastname: Sachdev
authors.affiliation: 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.
authors.forename: Margaret J
authors.initials: MJ
authors.lastname: Wright
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology*; D000679:Amygdala / Q000000981:diagnostic imaging / Q000473:pathology*; D001057:Apolipoproteins E / Q000235:genetics; D016022:Case-Control Studies; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D056726:Genetic Association Studies; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D008875:Middle Aged; D011971:Receptors, Immunologic / Q000235:genetics; D012306:Risk; D055815:Young Adult
chemical_list: D001057:Apolipoproteins E; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; C498715:TREM2 protein, human
keywords: APOE; Alzheimer's disease; Amygdala; Hippocampus; Polygenic risk score; TREM2