期刊
NEUROBIOLOGY OF AGING
卷 39, 期 -, 页码 -出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2015.11.017
关键词
TOMM40; Cognition; Aging; Retrotransposon; APOE; Expression
资金
- Medical Research Council [110577]
- BBSRC [BB/F022441/1] Funding Source: UKRI
- MRC [G0900753, G0901461, G0100594, MR/K002279/1, MC_PC_12018, G0600237] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/F022441/1] Funding Source: researchfish
- Medical Research Council [MC_PC_12018] Funding Source: researchfish
The Translocase of Outer Mitochondrial Membrane 40 Homolog and Apolipoprotein E (TOMM40-APOE) locus has been associated with a number of age-related phenotypes in humans including nonpathologic cognitive aging, late-onset Alzheimer's disease, and longevity. Here, we investigate the influence of the TOMM40 intron 6 poly-T variant (rs10524523) on TOMM40 gene expression and cognitive abilities and decline in a cohort of 1613 community-dwelling elderly volunteers who had been followed for changes in cognitive functioning over a period of 14 years (range = 12-18 years). We showed that the shorter length poly-T variants were found to act as a repressor of luciferase gene expression in reporter gene constructs. Expression was reduced to approximately half of that observed for the very long variant. We further observed that the shorter poly-T variant was significantly associated with reduced vocabulary ability and a slower rate of vocabulary decline with age compared to the very long poly-T variants. No significant associations were observed for memory, fluid intelligence or processing speed, although the direction of effect, where the short variant was correlated with reduced ability and slower rate of decline was observed for all tests. Our results indicate that the poly-T variant has the ability to interact with transcription machinery and differentially modulate reporter gene expression and influence vocabulary ability and decline with age. (C) 2016 Elsevier Inc. All rights reserved.
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