期刊
NEUROLOGY
卷 75, 期 10, 页码 874-880出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1212/WNL.0b013e3181f11deb
关键词
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资金
- NIH/NIA [R01 AG018386, RO1 AG018384, RO1 AG022381, RO1 AG022982, R01 AG018384, R01 AG022381, R01 AG022982]
- GE Healthcare
- NIH [R01MH079752-04, P50MH081755-03, R01AG031224-02, R01EB009282-02, R01AG012674-12, P50AG005131-26, P50DA026306-01A1, RC2DA029475-01, R01AG022381-07, NIAID 1UH2AI083263, NIDA U01 DA024413, NICHD R01 049685, NRSA T32 MH20030, NIMH R01 NIA 022982, NIDA R01 DA23668]
- UC San Diego Academic Senate
- VA VISN 22 Mental Illness Research Education and Clinical Center
- Ellison Medical Foundation
- US Department of Veterans Affairs
- Alzheimer's Association
- Massachusetts Department of Mental Health, UCLA
- Sidney Baer Foundation
Background: The APOE epsilon 4 allele is an established risk factor for Alzheimer disease (AD), yet findings are mixed for how early its effects are manifest. One reason for the mixed results could be the presence of interaction effects with other AD risk factors. Increasing evidence indicates that testosterone may play a significant role in the development of AD. The aim of the present study was to examine the potential interaction of testosterone and APOE genotype with respect to hippocampal volume in middle age. Methods: Participants were men from the Vietnam Era Twin Study of Aging (n = 375). The mean age was 55.9 years (range 51-59). Between-group comparisons were performed utilizing a hierarchical linear mixed model that adjusted for the nonindependence of twin data. Results: A significant interaction was observed between testosterone and APOE genotype (epsilon 4-negative vs epsilon 4-positive). Those with both low testosterone (>= 1 SD below the mean) and an epsilon 4-positive status had the smallest hippocampal volumes, although comparisons with normal testosterone groups were not significant. However, individuals with low testosterone and epsilon 4-negative status had significantly larger hippocampal volumes relative to all other groups. A main effect of APOE genotype on hippocampal volume was observed, but only when the APOE-by-testosterone interaction was present. Conclusions: These findings demonstrate an interaction effect between testosterone and the APOE epsilon 4 allele on hippocampal volume in middle-aged men, and they may suggest 2 low testosterone subgroups. Furthermore, these results allude to potential gene-gene interactions between APOE and either androgen receptor polymorphisms or genes associated with testosterone production. Neurology (R) 2010; 75: 874-880
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