Please use this identifier to cite or link to this item: http://hdl.handle.net/1893/27460
Appears in Collections:Psychology Journal Articles
Peer Review Status: Refereed
Title: Alzheimer's disease susceptibility genes APOE and TOMM40, and brain white matter integrity in the Lothian Birth Cohort 1936
Author(s): Lyall, Donald M
Harris, Sarah E
Bastin, Mark E
Muñoz Maniega, Susana
Murray, Catherine
Lutz, Michael W
Saunders, Ann M
Roses, Allen D
Valdés Hernández, Maria del C
Royle, Natalie A
Starr, John M
Porteous, David J
Wardlaw, Joanna M
Deary, Ian J
Keywords: White matter
Cognitive ageing
Diffusion MRI
Tractography
APOE
TOMM40
Alzheimer's disease
Issue Date: 30-Jun-2014
Citation: Lyall DM, Harris SE, Bastin ME, Muñoz Maniega S, Murray C, Lutz MW, Saunders AM, Roses AD, Valdés Hernández MdC, Royle NA, Starr JM, Porteous DJ, Wardlaw JM & Deary IJ (2014) Alzheimer's disease susceptibility genes APOE and TOMM40, and brain white matter integrity in the Lothian Birth Cohort 1936, Neurobiology of Aging, 35 (6), pp. 1513.e25-1513.e33. https://doi.org/10.1016/j.neurobiolaging.2014.01.006.
Abstract: Apolipoprotein E (APOE) ε genotype has previously been significantly associated with cognitive, brain imaging, and Alzheimer's disease-related phenotypes (e.g., age of onset). In the TOMM40 gene, the rs10524523 (“523”) variable length poly-T repeat polymorphism has more recently been associated with similar phenotypes, although the allelic directions of these associations have varied between initial reports. Using diffusion magnetic resonance imaging tractography, the present study aimed to investigate whether there are independent effects of apolipoprotein E (APOE) and TOMM40 genotypes on human brain white matter integrity in a community-dwelling sample of older adults, the Lothian Birth Cohort 1936 (mean age = 72.70 years, standard deviation = 0.74, N approximately = 640–650; for most analyses). Some nominally significant effects were observed (i.e., covariate-adjusted differences between genotype groups at p < 0.05). For APOE, deleterious effects of ε4 “risk” allele presence (vs. absence) were found in the right ventral cingulum and left inferior longitudinal fasciculus. To test for biologically independent effects of the TOMM40 523 repeat, participants were stratified into APOE genotype subgroups, so that any significant effects could not be attributed to APOE variation. In participants with the APOE ε3/ε4 genotype, effects of TOMM40 523 status were found in the left uncinate fasciculus, left rostral cingulum, left ventral cingulum, and a general factor of white matter integrity. In all 4 of these tractography measures, carriers of the TOMM40 523 “short” allele showed lower white matter integrity when compared with carriers of the “long” and “very-long” alleles. Most of these effects survived correction for childhood intelligence test scores and vascular disease history, though only the effect of TOMM40 523 on the left ventral cingulum integrity survived correction for false discovery rate. The effects of APOE in this older population are more specific and restricted compared with those reported in previous studies, and the effects of TOMM40 on white matter integrity appear to be novel, although replication is required in large independent samples.
DOI Link: 10.1016/j.neurobiolaging.2014.01.006
Rights: Copyright 2014 The Authors. Published by Elsevier Inc. Open access under CC BY license (https://creativecommons.org/licenses/by/3.0/)

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