Alzheimer's disease susceptibility genes APOE and TOMM40, and hippocampal volumes in the Lothian birth cohort 1936.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • 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

Published Date

  • January 2013

Published In

Volume / Issue

  • 8 / 11

Start / End Page

  • e80513 -

PubMed ID

  • 24260406

Pubmed Central ID

  • 24260406

Electronic International Standard Serial Number (EISSN)

  • 1932-6203

International Standard Serial Number (ISSN)

  • 1932-6203

Digital Object Identifier (DOI)

  • 10.1371/journal.pone.0080513

Language

  • eng