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
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.

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