Gender Modulates the APOE 4 Effect in Healthy Older Adults: Convergent Evidence from Functional Brain Connectivity and Spinal Fluid Tau Levels
Year: 2012
Type: article
Study design: Observational Study
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.
Source: Journal of Neuroscience
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: Foundation for the National Institutes of Health, Larry L. Hillblom Foundation, Alzheimer's Disease Neuroimaging Initiative, Northern California Institute for Research and Education, National Institutes of Health, University of California, Los Angeles, University of California, San Diego, Canadian Institutes of Health Research, National Institute on Aging, National Institute of Neurological Disorders and Stroke, National Center for Advancing Translational Sciences
Awards: G104586243, Alzheimer's Disease Neuroimaging Initiative, G2152643862, G2835601961, G29951154, G3705772492, G3908963977, G4401988282, Development of Resting-State fMRI as a Biomarker for Alzheimers Disease, G6451738334, The Frontotemporal Lobar Degeneration Neuroimaging Initiative, Arizona Alzheimer's Disease Core Center, G7414321945, Boston University Alzheimer's Disease Center, Kentucky Center for Clinical and Translational Science, Alzheimer's Disease Cooperative Study, G9000039018, G9000074849, G9000122335, Frontotemporal Dementia: Genes, Images, and Emotions, Biological predictors of brain aging trajectories, Kentucky Center for Clinical and Translational Science
OpenAlex ID: W2101009033