Gender Modulates the APOE epsilon 4 Effect in Healthy Older Adults: Convergent Evidence from Functional Brain Connectivity and Spinal Fluid Tau Levels JOURNAL OF NEUROSCIENCE Damoiseaux, J. S., Seeley, W. W., Zhou, J., Shirer, W. R., Coppola, G., Karydas, A., Rosen, H. J., Miller, B. L., Kramer, J. H., Greicius, M. D. 2012; 32 (24): 8254-8262


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 e4 carriers compared with e3 homozygotes. More important, further testing revealed a significant interaction between APOE genotype and gender in the precuneus, a major default mode hub. Female e4 carriers showed significantly reduced default mode connectivity compared with either female e3 homozygotes or male e4 carriers, whereas male e4 carriers differed minimally from male e3 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 e4 allele among women with Alzheimer's disease and, critically, demonstrate that this interaction between APOE genotype and gender is detectable in the preclinical period.

View details for DOI 10.1523/JNEUROSCI.0305-12.2012

View details for Web of Science ID 000305295600017

View details for PubMedID 22699906

View details for PubMedCentralID PMC3394933