RT Journal Article
SR Electronic
T1 Gender Modulates the <em>APOE</em> ε4 Effect in Healthy Older Adults: Convergent Evidence from Functional Brain Connectivity and Spinal Fluid Tau Levels
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 8254
OP 8262
DO 10.1523/JNEUROSCI.0305-12.2012
VO 32
IS 24
A1 Jessica S. Damoiseaux
A1 William W. Seeley
A1 Juan Zhou
A1 William R. Shirer
A1 Giovanni Coppola
A1 Anna Karydas
A1 Howard J. Rosen
A1 Bruce L. Miller
A1 Joel H. Kramer
A1 Michael D. Greicius
YR 2012
UL http://www.jneurosci.org/content/32/24/8254.abstract
AB 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.