Article

Gender modulates the APOE ε4 effect in healthy older adults: convergent evidence from functional brain connectivity and spinal fluid tau levels.

Functional Imaging in Neuropsychiatric Disorders Laboratory, Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California 94305, USA.
Journal of Neuroscience (impact factor: 7.11). 06/2012; 32(24):8254-62. DOI:10.1523/JNEUROSCI.0305-12.2012 pp.8254-62
Source: PubMed

ABSTRACT We examined whether the effect of the apolipoprotein E (APOE) genotype on functional brain connectivity is modulated by gender in healthy older human adults. Our results confirm significantly decreased connectivity in the default mode network in healthy older APOE ε4 carriers compared with ε3 homozygotes. More important, further testing revealed a significant interaction between APOE genotype and gender in the precuneus, a major default mode hub. Female ε4 carriers showed significantly reduced default mode connectivity compared with either female ε3 homozygotes or male ε4 carriers, whereas male ε4 carriers differed minimally from male ε3 homozygotes. An additional analysis in an independent sample of healthy elderly using an independent marker of Alzheimer's disease, i.e., spinal fluid levels of tau, provided corresponding evidence for this gender-by-APOE interaction. Together, these results converge with previous work showing a higher prevalence of the ε4 allele among women with Alzheimer's disease and, critically, demonstrate that this interaction between APOE genotype and gender is detectable in the preclinical period.

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Keywords

additional analysis
 
Alzheimer's disease
 
APOE genotype
 
corresponding evidence
 
default mode connectivity
 
default mode network
 
female ε3 homozygotes
 
Female ε4 carriers
 
functional brain connectivity
 
gender-by-APOE interaction
 
healthy elderly
 
higher prevalence
 
independent marker
 
major default mode hub
 
male ε3 homozygotes
 
male ε4 carriers
 
preclinical period
 
significant interaction
 
spinal fluid levels
 
ε3 homozygotes