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Cited by 267Dementia and Cognitive Impairment ResearchFunctional Brain Connectivity StudiesAlzheimer's disease research and treatments

Gender Modulates the APOE 4 Effect in Healthy Older Adults: Convergent Evidence from Functional Brain Connectivity and Spinal Fluid Tau Levels

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Damoiseaux, J. S., Seeley, W. W., Zhou, J., Shirer, W. R., Coppola, G., Karydas, A., Rosen, H. J., Miller, B. L. +3 more·2012·Journal of Neuroscience
DOI 10.1523/jneurosci.0305-12.2012PMC PMC3394933
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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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Authors
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., & Initiative, F. T. A. D. N.
Affiliations
  • Stanford Medicine (US)
  • University of California, San Francisco (US)
  • National University of Singapore (SG)
  • University of California, Los Angeles (US)
ORCID
Venue
Journal of Neuroscience
Publisher
Society for Neuroscience
Published
2012-06-13
Volume
32
Issue
24
Pages
8254-8262
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
DOI
10.1523/jneurosci.0305-12.2012
PMC
PMC3394933
OpenAlex
W2101009033
Cited by
267
References
58
Citations by year
2026: 10 · 2025: 25 · 2024: 17 · 2023: 15 · 2022: 24 · 2021: 23 · 2020: 22 · 2019: 24 · 2018: 20 · 2017: 12 · 2016: 21 · 2015: 22 · 2014: 13 · 2013: 16 · 2012: 3
FWCI
12.34
Type
journal article
Language
en
Open access
Locations
  • Journal of Neuroscience (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
  • National University of Singapore (submittedVersion)
Funders
  • Foundation for the National Institutes of Health (U01AG024904, Grant U01 AG024904, NS073498, AG024904)
  • Larry L. Hillblom Foundation
  • Alzheimer's Disease Neuroimaging Initiative (U01AG024904, AG024904)
  • Northern California Institute for Research and Education (U01 AG024904)
  • National Institutes of Health (3u01ag024904-10s2, UL1TR000117, U01-AG024904, Grant U01 AG024904, AG024904, AG032306, UL1TR001998)
  • University of California, Los Angeles
  • University of California, San Diego
  • Canadian Institutes of Health Research (U01 AG024904)
  • National Institute on Aging (U01-AG-024904, AG032306, R01AG032306, P30AG019610, P30AG013846, U19AG010483, P01AG019724, R01AG032289)
  • National Institute of Neurological Disorders and Stroke (R01NS073498, NS073498)
  • National Center for Advancing Translational Sciences
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Keywords
APOE ε4, APOE genotype, sex differences, default mode network, brain functional connectivity, precuneus, cerebrospinal fluid tau, Alzheimer's disease, preclinical Alzheimer's disease, older adults, genetic risk
MeSH terms
Aged, Alleles, Brain, Female, Genotype, Homozygote, Humans, Magnetic Resonance Imaging, Male, Neural Pathways, Neuropsychological Tests, Sex Characteristics, Databases, Factual, tau Proteins, Nerve Fibers, Unmyelinated, Apolipoprotein E3, Apolipoprotein E4, Functional Neuroimaging

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