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| PMID |
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| TITLE |
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| The effect of increased genetic risk for Alzheimer's disease on hippocampal and amygdala volume. |
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| ABSTRACT |
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| 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. |
| Copyright © 2016 Elsevier Inc. All rights reserved. |
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| DATE PUBLISHED |
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| HISTORY |
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| PUBSTATUS |
PUBSTATUSDATE |
| received |
2015/09/16 |
| revised |
2015/12/04 |
| accepted |
2015/12/29 |
| aheadofprint |
2016/01/11 |
| entrez |
2016/03/15 06:00 |
| pubmed |
2016/03/15 06:00 |
| medline |
2016/03/15 06:00 |
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| AUTHORS |
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| NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
| Lupton MK |
|
Lupton |
Michelle K |
MK |
|
Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. Electronic address: Michelle.Lupton@qimrberghofer.edu.au. |
| Strike L |
|
Strike |
Lachlan |
L |
|
Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia; Queensland Brain Institute, The University of Queensland, St Lucia, Queensland, Australia. |
| Hansell NK |
|
Hansell |
Narelle K |
NK |
|
Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia; Queensland Brain Institute, The University of Queensland, St Lucia, Queensland, Australia. |
| Wen W |
|
Wen |
Wei |
W |
|
Centre for Healthy Brain Ageing, University of New South Wales, Sydney, New South Wales, Australia. |
| Mather KA |
|
Mather |
Karen A |
KA |
|
Centre for Healthy Brain Ageing, University of New South Wales, Sydney, New South Wales, Australia. |
| Armstrong NJ |
|
Armstrong |
Nicola J |
NJ |
|
Mathematics and Statistics, Murdoch University, Perth, Western Australia, Australia. |
| Thalamuthu A |
|
Thalamuthu |
Anbupalam |
A |
|
Centre for Healthy Brain Ageing, University of New South Wales, Sydney, New South Wales, Australia. |
| McMahon KL |
|
McMahon |
Katie L |
KL |
|
Centre for Advanced Imaging, University of Queensland, Brisbane, Queensland, Australia. |
| de Zubicaray GI |
|
de Zubicaray |
Greig I |
GI |
|
Faculty of Health and Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Brisbane, Queensland, Australia. |
| Assareh AA |
|
Assareh |
Amelia A |
AA |
|
Centre for Healthy Brain Ageing, University of New South Wales, Sydney, New South Wales, Australia. |
| Simmons A |
|
Simmons |
Andrew |
A |
|
Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. |
| Proitsi P |
|
Proitsi |
Petroula |
P |
|
Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. |
| Powell JF |
|
Powell |
John F |
JF |
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Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. |
| Montgomery GW |
|
Montgomery |
Grant W |
GW |
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Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. |
| Hibar DP |
|
Hibar |
Derrek P |
DP |
|
Imaging Genetics Center, Keck School of Medicine, University of Southern California, Marina del Ray, CA, USA. |
| Westman E |
|
Westman |
Eric |
E |
|
Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Alzheimer's Disease Research Centre, Karolinska Institute, Stockholm, Sweden. |
| Tsolaki M |
|
Tsolaki |
Magda |
M |
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Memory and Dementia Centre, Aristotle University of Thessaloniki, Thessaloniki, Greece. |
| Kloszewska I |
|
Kloszewska |
Iwona |
I |
|
Department of Old Age Psychiatry & Psychotic Disorders, Medical University of Lodz, Lodz, Poland. |
| Soininen H |
|
Soininen |
Hilkka |
H |
|
Department of Neurology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland. |
| Mecocci P |
|
Mecocci |
Patrizia |
P |
|
Section of Gerontology and Geriatrics, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy. |
| Velas B |
|
Velas |
Bruno |
B |
|
Gerontopole, CHU, UMR INSERM 1027, University of Toulouse, France. |
| Lovestone S |
|
Lovestone |
Simon |
S |
|
Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK; Department of Psychiatry, Warneford Hospital, University of Oxford, Oxford, UK. |
|
Alzheimer's Disease Neuroimaging Initiative |
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| Brodaty H |
|
Brodaty |
Henry |
H |
|
Centre for Healthy Brain Ageing, University of New South Wales, Sydney, New South Wales, Australia. |
| Ames D |
|
Ames |
David |
D |
|
National Ageing Research Institute, Parkville, Victoria, Australia; Academic Unit for Psychiatry of Old Age, University of Melbourne, Kew, Victoria, Australia. |
| Trollor JN |
|
Trollor |
Julian N |
JN |
|
Centre for Healthy Brain Ageing, University of New South Wales, Sydney, New South Wales, Australia. |
| Martin NG |
|
Martin |
Nicholas G |
NG |
|
Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. |
| Thompson PM |
|
Thompson |
Paul M |
PM |
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Imaging Genetics Center, Keck School of Medicine, University of Southern California, Marina del Ray, CA, USA. |
| Sachdev PS |
|
Sachdev |
Perminder S |
PS |
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Centre for Healthy Brain Ageing, University of New South Wales, Sydney, New South Wales, Australia. |
| Wright MJ |
|
Wright |
Margaret J |
MJ |
|
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. |
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| INVESTIGATORS |
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| JOURNAL |
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| VOLUME: 40 |
| ISSUE: |
| TITLE: Neurobiology of aging |
| ISOABBREVIATION: Neurobiol. Aging |
| YEAR: 2016 |
| MONTH: Apr |
| DAY: |
| MEDLINEDATE: |
| SEASON: |
| CITEDMEDIUM: Internet |
| ISSN: 1558-1497 |
| ISSNTYPE: Electronic |
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| MEDLINE JOURNAL |
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| MEDLINETA: Neurobiol Aging |
| COUNTRY: United States |
| ISSNLINKING: 0197-4580 |
| NLMUNIQUEID: 8100437 |
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| PUBLICATION TYPE |
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| PUBLICATIONTYPE TEXT |
| Journal Article |
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| COMMENTS AND CORRECTIONS |
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| GRANTS |
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| GRANTID |
AGENCY |
COUNTRY |
| R01 AG040060 |
NIA NIH HHS |
United States |
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| GENERAL NOTE |
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| KEYWORDS |
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| KEYWORD |
| APOE |
| Alzheimer's disease |
| Amygdala |
| Hippocampus |
| Polygenic risk score |
| TREM2 |
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| MESH HEADINGS |
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| SUPPLEMENTARY MESH |
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| GENE SYMBOLS |
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| CHEMICALS |
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| OTHER ID's |
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