Two-thirds of patients with Alzheimer disease (AD) are women, and sex differences in AD pathology have been observed, yet little is known about the role of sex chromosomes in AD. New research suggests that X-linked gene expression modifies AD risk in a sex-specific manner. This knowledge could aid the development of precision medicine approaches for AD.
This is a preview of subscription content, access via your institution
Access options
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$29.99 / 30 days
cancel any time
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
References
Ferretti, M. T., Schumacher Dimech, A. & Santuccione Chadha, A. (eds) Sex and Gender Differences in Alzheimer’s Disease 1st edn (Academic Press, 2021).
Villa, A. et al. Sex-specific features of microglia from adult mice. Cell Rep. 23, 3501–3511 (2018).
Abd-Elrahman, K. S. et al. Aβ oligomers induce pathophysiological mGluR5 signaling in Alzheimer’s disease model mice in a sex-selective manner. Sci. Signal. 13, eabd2494 (2021).
Bernabeu, E. et al. Sex differences in genetic architecture in the UK Biobank. Nat. Genet. 53, 1283–1289 (2021).
Trabzuni, D. et al. Widespread sex differences in gene expression and splicing in the adult human brain. Nat. Commun. 4, 2771 (2013).
Davis, E. J. et al. Sex-specific association of the X chromosome with cognitive change and tau pathology in aging and Alzheimer disease. JAMA Neurol. https://doi.org/10.1001/jamaneurol.2021.2806 (2021).
Barnes, L. L. et al. Sex differences in the clinical manifestations of Alzheimer disease pathology. Arch. Gen. Psychiatry 62, 685–691 (2005).
van Maurik, I. S. et al. Personalized risk for clinical progression in cognitively normal subjects — the ABIDE project. Alzheimers Res. Ther. 11, 33 (2019).
Sundermann, E. E. et al. Women’s higher brain metabolic rate compensates for early Alzheimer’s pathology. Alzheimers Dement. 12, e12121 (2020).
Fan, H. et al. X inactivation and escape: epigenetic and structural features. Front. Cell Dev. Biol. 7, 219 (2019).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
M.T.F. is the co-founder and Chief Scientific Officer of the non-profit organization ‘Women’s Brain Project’. She has received personal fees from Eli Lilly for work unrelated to this article. A.S.C. is an official employee of Biogen International and works as Head of Stakeholder Engagement for Alzheimer disease at Biogen. She is also co-founder and CEO of the Women’s Brain Project. This article represents her personal view and not the position of any group with which she is associated.
Additional information
Related links
Women’s Brain Project: https://www.womensbrainproject.com/
Rights and permissions
About this article
Cite this article
Ferretti, M.T., Santuccione Chadha, A. The missing X factor in Alzheimer disease. Nat Rev Neurol 17, 727–728 (2021). https://doi.org/10.1038/s41582-021-00573-x
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41582-021-00573-x
