The effect of increased genetic risk for Alzheimer's disease on hippocampal and amygdala volume.
Τίτλος | The effect of increased genetic risk for Alzheimer's disease on hippocampal and amygdala volume. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Lupton, M. K., Strike L., Hansell N. K., Wen W., Mather K. A., Armstrong N. J., Thalamuthu A., McMahon K. L., de Zubicaray G. I., Assareh A. A., Simmons A., Proitsi P., Powell J. F., Montgomery G. W., Hibar D. P., Westman E., Tsolaki M., Kloszewska I., Soininen H., Mecocci P., Velas B., Lovestone S., Brodaty H., Ames D., Trollor J. N., Martin N. G., Thompson P. M., Sachdev P. S., & Wright M. J. |
Corporate Authors | Alzheimer's Disease Neuroimaging Initiative |
Journal | Neurobiol Aging |
Volume | 40 |
Pagination | 68-77 |
Date Published | 2016 Apr |
ISSN | 1558-1497 |
Λέξεις κλειδιά | Adolescent, Adult, Aged, Aged, 80 and over, Alzheimer Disease, Amygdala, Apolipoproteins E, Case-Control Studies, Cognitive Dysfunction, Cohort Studies, Female, Genetic Association Studies, Hippocampus, Humans, Magnetic Resonance Imaging, Male, Membrane Glycoproteins, Middle Aged, Receptors, Immunologic, Risk, Young Adult |
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. |
DOI | 10.1016/j.neurobiolaging.2015.12.023 |
Alternate Journal | Neurobiol. Aging |
PubMed ID | 26973105 |
PubMed Central ID | PMC4883003 |
Grant List | 082604/2/07/Z / / Wellcome Trust / United Kingdom 503480 / / Medical Research Council / United Kingdom U24 AG021886 / AG / NIA NIH HHS / United States R01 AG040060 / AG / NIA NIH HHS / United States U01 AG032984 / AG / NIA NIH HHS / United States 167 / / Alzheimer's Society / United Kingdom U01 AG024904 / AG / NIA NIH HHS / United States U01 AG016976 / AG / NIA NIH HHS / United States P30 AG013846 / AG / NIA NIH HHS / United States P50 AG005136 / AG / NIA NIH HHS / United States R01 HL105756 / HL / NHLBI NIH HHS / United States P50 AG047266 / AG / NIA NIH HHS / United States UL1 TR001422 / TR / NCATS NIH HHS / United States U54 EB020403 / EB / NIBIB NIH HHS / United States R01 HD050735 / HD / NICHD NIH HHS / United States R01 AG033193 / AG / NIA NIH HHS / United States TL1 TR000096 / TR / NCATS NIH HHS / United States AG081220 / AG / NIA NIH HHS / United States N01-AG-12100 / AG / NIA NIH HHS / United States |