Please use this identifier to cite or link to this item: http://hdl.handle.net/1893/27555
Appears in Collections:Psychology Journal Articles
Peer Review Status: Refereed
Title: Alzheimer’s Disease Susceptibility Genes APOE and TOMM40, and Hippocampal Volumes in the Lothian Birth Cohort 1936
Author(s): Lyall, Donald M
Royle, Natalie A
Harris, Sarah E
Bastin, Mark E
Maniega, Susana Muñoz
Murray, Catherine
Lutz, Michael W
Saunders, Ann M
Roses, Allen D
del Valdés Hernández, Maria C
Starr, John M
Porteous, David J
Wardlaw, Joanna M
Deary, Ian J
Issue Date: 15-Nov-2013
Date Deposited: 6-Jul-2018
Citation: Lyall DM, Royle NA, Harris SE, Bastin ME, Maniega SM, Murray C, Lutz MW, Saunders AM, Roses AD, del Valdés Hernández MC, Starr JM, Porteous DJ, Wardlaw JM & Deary IJ (2013) Alzheimer’s Disease Susceptibility Genes APOE and TOMM40, and Hippocampal Volumes in the Lothian Birth Cohort 1936. PLoS ONE, 8 (11), p. e80513. https://doi.org/10.1371/journal.pone.0080513
Abstract: The APOE ε and TOMM40 rs10524523 (‘523’) variable length poly-T repeat gene loci have been significantly and independently associated with Alzheimer’s disease (AD) related phenotypes such as age of clinical onset. Hippocampal atrophy has been significantly associated with memory impairment, a characteristic of AD. The current study aimed to test for independent effects of APOE ε and TOMM40 ‘523’ genotypes on hippocampal volumes as assessed by brain structural MRI in a relatively large sample of community-dwelling older adults. As part of a longitudinal study of cognitive ageing, participants in the Lothian Birth Cohort 1936 underwent genotyping for APOE ε2/ε3/ε4 status and TOMM40 ‘523’ poly-T repeat length, and detailed structural brain MRI at a mean age of 72.7 years (standard deviation = 0.7, N range = 624 to 636). No significant effects of APOE ε or TOMM40 523 genotype were found on hippocampal volumes when analysed raw, or when adjusted for either intracranial or total brain tissue volumes. In summary, in a large community-dwelling sample of older adults, we found no effects of APOE ε or TOMM40 523 genotypes on hippocampal volumes. This is discrepant with some previous reports of significant association between APOE and left/right hippocampal volumes, and instead echoes other reports that found no association. Previous significant findings may partly reflect type 1 error. Future studies should carefully consider: 1) their specific techniques in adjusting for brain size; 2) assessing more detailed sub-divisions of the hippocampal formation; and 3) testing whether significant APOE-hippocampal associations are independent of generalised brain atrophy.
DOI Link: 10.1371/journal.pone.0080513
Rights: © 2013 Lyall et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Licence URL(s): http://creativecommons.org/licenses/by/3.0/

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