Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2014 Jun;8(2):262-73.
doi: 10.1007/s11682-013-9272-x.

Apolipoprotein E, gender, and Alzheimer's disease: an overlooked, but potent and promising interaction

Leo Ungar  1 , Andre Altmann, Michael D Greicius
Affiliations
Review

Apolipoprotein E, gender, and Alzheimer's disease: an overlooked, but potent and promising interaction

Leo Ungar et al. Brain Imaging Behav. 2014 Jun.

Abstract

Alzheimer's disease (AD) is an increasingly prevalent, fatal neurodegenerative disease that has proven resistant, thus far, to all attempts to prevent it, forestall it, or slow its progression. The ε4 allele of the Apolipoprotein E gene (APOE4) is a potent genetic risk factor for sporadic and late-onset familial AD. While the link between APOE4 and AD is strong, many expected effects, like increasing the risk of conversion from MCI to AD, have not been widely replicable. One critical, and commonly overlooked, feature of the APOE4 link to AD is that several lines of evidence suggest it is far more pronounced in women than in men. Here we review previous literature on the APOE4 by gender interaction with a particular focus on imaging-related studies.

PubMed Disclaimer

Figures

Figure 1
Figure 1. APOE4 risk is greater in women
Compared to background risk in APOE3 homozygotes, female APOE3/4 heterozygotes’ odds ratio peaks near 4 whereas the odds ratio in male APOE3/4 heterozygotes barely exceeds 1. The odds ratio for both men and women APOE4 homozygotes peaks near 10 though remains somewhat higher in women. (This is adapted from Figure 2 in the meta-analysis by Farrer and colleagues).
Figure 2
Figure 2
Gender modulates the APOE effect on default mode network connectivity. An ApoE by gender interaction was found in the precuneus region of the default mode network. The bar graph shows the mean parameter estimates for this cluster, for male and female E3 homozygotes and male and female E4 carriers. The greatest reduction was observed in the female 4 carriers. (This is adapted from Figure 3 of Damoiseaux et al.)
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. 2012 Alzheimer’s disease facts and figures. Alzheimers Dement. 2012;8(2):131–168. doi: 10.1016/j.jalz.2012.02.001. - DOI - PubMed
    1. Adamson MM, Hutchinson JB, Shelton AL, Wagner AD, Taylor JL. Reduced hippocampal activity during encoding in cognitively normal adults carrying the APOE varepsilon4 allele. Neuropsychologia. 2011;49(9):2448–2455. doi: 10.1016/j.neuropsychologia.2011.04.022. - DOI - PMC - PubMed
    1. Aisen PS. Clinical trial methodologies for disease-modifying therapeutic approaches. Neurobiol Aging. 2011;32(Suppl 1):S64–66. doi: 10.1016/j.neurobiolaging.2011.09.008. - DOI - PMC - PubMed
    1. Aizenstein HJ, Nebes RD, Saxton JA, Price JC, Mathis CA, Tsopelas ND, Klunk WE. Frequent amyloid deposition without significant cognitive impairment among the elderly. Arch Neurol. 2008;65(11):1509–1517. doi: 10.1001/archneur.65.11.1509. - DOI - PMC - PubMed
    1. Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, Phelps CH. The diagnosis of mild cognitive impairment due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7(3):270–279. doi: 10.1016/j.jalz.2011.03.008. - DOI - PMC - PubMed

Substances