Alzheimer’s disease susceptibility genes APOE and TOMM40, and hippocampal Volumes in the Lothian Birth Cohort 1936

Lyall, D. M. et al. (2013) Alzheimer’s disease susceptibility genes APOE and TOMM40, and hippocampal Volumes in the Lothian Birth Cohort 1936. PLoS ONE, 8(11), e80513. (doi: 10.1371/journal.pone.0080513) (PMID:24260406) (PMCID:PMC3829876)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Lyall, Dr Donald
• Authors: Lyall, D. M., Royle, N. A., Harris, S. E., Bastin, M. E., Maniega, S. M., Murray, C., Lutz, M. W., Saunders, A. M., Roses, A. D., del Valdés Hernández, M. C., Starr, J. M., Porteous, D. J., Wardlaw, J. M., and Deary, I. J.
• College/School: College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Public Health
• Journal Name: PLoS ONE
• Publisher: Public Library of Science
• ISSN: 1932-6203
• Copyright Holders: Copyright © 2013 The Authors
• First Published: First published in PLoS One 8(11):e80513
• Publisher Policy: Reproduced under a Creative Commons License