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; Bruno Velas; Simon Lovestone; Alzheimer's Disease Neuroimaging Initiative; Henry Brodaty; David Ames; Julian N Trollor; Nicholas G Martin; Paul M Thompson; Perminder S Sachdev; Margaret J Wright

doi:10.1016/j.neurobiolaging.2015.12.023

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

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

Authors

Michelle K Lupton¹, Lachlan Strike², Narelle K Hansell², Wei Wen³, Karen A Mather³, Nicola J Armstrong⁴, Anbupalam Thalamuthu³, Katie L McMahon⁵, Greig I de Zubicaray⁶, Amelia A Assareh³, Andrew Simmons⁷, Petroula Proitsi⁷, John F Powell⁷, Grant W Montgomery⁸, Derrek P Hibar⁹, Eric Westman¹⁰, Magda Tsolaki¹¹, Iwona Kloszewska¹², Hilkka Soininen¹³, Patrizia Mecocci¹⁴, Bruno Velas¹⁵, Simon Lovestone¹⁶; Alzheimer's Disease Neuroimaging Initiative; Henry Brodaty³, David Ames¹⁷, Julian N Trollor³, Nicholas G Martin⁸, Paul M Thompson⁹, Perminder S Sachdev³, Margaret J Wright¹⁸

Affiliations

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.

PMID: 26973105
PMCID: PMC4883003
DOI: 10.1016/j.neurobiolaging.2015.12.023

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.

Keywords: APOE; Alzheimer's disease; Amygdala; Hippocampus; Polygenic risk score; TREM2.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Adolescent
Adult
Aged
Aged, 80 and over
Alzheimer Disease / diagnostic imaging
Alzheimer Disease / genetics*
Alzheimer Disease / pathology*
Amygdala / diagnostic imaging
Amygdala / pathology*
Apolipoproteins E / genetics
Case-Control Studies
Cognitive Dysfunction / diagnostic imaging
Cognitive Dysfunction / genetics
Cognitive Dysfunction / pathology
Cohort Studies
Female
Genetic Association Studies*
Hippocampus / diagnostic imaging
Hippocampus / pathology*
Humans
Magnetic Resonance Imaging
Male
Membrane Glycoproteins / genetics
Middle Aged
Receptors, Immunologic / genetics
Risk
Young Adult

Substances

Apolipoproteins E
Membrane Glycoproteins
Receptors, Immunologic
TREM2 protein, human

Abstract

Publication types

MeSH terms

Substances

Grants and funding