Document Detail


Testosterone modifies the effect of APOE genotype on hippocampal volume in middle-aged men.
MedLine Citation:
PMID:  20819998     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: The APOE epsilon4 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 (epsilon4-negative vs epsilon4-positive). Those with both low testosterone (> or =1 SD below the mean) and an epsilon4-positive status had the smallest hippocampal volumes, although comparisons with normal testosterone groups were not significant. However, individuals with low testosterone and epsilon4-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 epsilon4 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.
Authors:
M S Panizzon; R Hauger; A M Dale; L J Eaves; L T Eyler; B Fischl; C Fennema-Notestine; C E Franz; M D Grant; A J Jak; K C Jacobson; M J Lyons; S P Mendoza; M C Neale; E C Prom-Wormley; L J Seidman; M T Tsuang; H Xian; W S Kremen
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Twin Study    
Journal Detail:
Title:  Neurology     Volume:  75     ISSN:  1526-632X     ISO Abbreviation:  Neurology     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-09-07     Completed Date:  2010-09-27     Revised Date:  2014-09-09    
Medline Journal Info:
Nlm Unique ID:  0401060     Medline TA:  Neurology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  874-80     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Aging / genetics
Alleles
Apolipoproteins E / genetics*,  metabolism
Genotype
Hippocampus / anatomy & histology*,  metabolism
Humans
Magnetic Resonance Imaging
Male
Middle Aged
Organ Size
Polymorphism, Genetic
Testosterone / blood*
United States
Veterans
Vietnam Conflict
Grant Support
ID/Acronym/Agency:
R01 AG018384/AG/NIA NIH HHS; R01 AG018386/AG/NIA NIH HHS; R01 AG018386/AG/NIA NIH HHS; R01 AG022381/AG/NIA NIH HHS; R01 AG022381/AG/NIA NIH HHS; R01 AG022982/AG/NIA NIH HHS
Chemical
Reg. No./Substance:
0/Apolipoproteins E; 3XMK78S47O/Testosterone
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