Key result
Female APOE e4 carriers showed significantly reduced posterior default mode network connectivity and higher CSF total tau levels compared to female e3 homozygotes and male e4 carriers.
Why the study?
Does gender modulate the effect of APOE ε4 genotype on functional brain connectivity and spinal fluid tau levels in healthy older adults?
Cross-Sectional (n=224)
Yes
Does gender modulate the effect of APOE ε4 genotype on functional brain connectivity and spinal fluid tau levels in healthy older adults?
Answers are grounded in this paper and cite their sources.
The interaction between APOE genotype and gender, with female ε4 carriers showing greater Alzheimer's-related brain changes, is detectable in the preclinical period.
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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Damoiseaux et al. (2012) conducted a cross-sectional in Healthy older adults (n=224). APOE e4 allele and female gender vs. APOE e3 homozygotes and male gender was evaluated on Interaction between APOE genotype and gender on posterior default mode network connectivity and cerebrospinal fluid total tau levels (p=0.024). Female APOE e4 carriers showed significantly reduced posterior default mode network connectivity and higher CSF total tau levels compared to female e3 homozygotes and male e4 carriers.
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