Abstract
Sex differences exist in the onset and progression of Alzheimer’s disease. Globally, women have a higher prevalence, while men with Alzheimer’s disease experience earlier mortality and more pronounced cognitive decline than women. The cause of sex differences in Alzheimer’s disease remains unclear. Accumulating evidence suggests the potential role of X-linked genetic factors in the sex difference of Alzheimer’s disease (AD). During embryogenesis, a remarkable process known as X-chromosome inactivation (XCI) occurs in females, leading to one of the X chromosomes undergoing transcriptional inactivation, which balances the effects of two X chromosomes in females. Nevertheless, certain genes exceptionally escape from XCI, which provides a basis for dual expression dosage of specific genes in females. Based on recent research findings, we explore key escape genes and their potential therapeutic use associated with Alzheimer’s disease. Also, we discuss their possible role in driving the sex differences in Alzheimer’s disease. This will provide new perspectives for precision medicine and gender-specific treatment of AD.
Funding source: China Postdoctoral Science Foundation
Award Identifier / Grant number: 2022M713476
Funding source: National Natural Science Foundation of China
Award Identifier / Grant number: No. 81673434
Award Identifier / Grant number: No. 82003968
Funding source: “Double First Class” University project
Award Identifier / Grant number: CPU2018GY22
Funding source: National Natural Science Foundation of China
Award Identifier / Grant number: Unassigned
Funding source: China Postdoctoral Science Foundation
Award Identifier / Grant number: Unassigned
Acknowledgments
This work was supported by the National Natural Science Foundation of China (No. 82003968, No. 81673434), “Double First Class” University project (CPU2018GY22) and China Postdoctoral Science Foundation, 2022M713476. Figure 1 was made with BioRender.com.
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Research ethics: Not applicable.
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Author contributions: The authors have accepted responsibility for the entire content of this manuscript and approved its submission.
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Competing interests: The authors state no conflict of interest.
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Research funding: This work was funded by the National Natural Science Foundation of China (No. 82003968, No. 81673434), “Double First Class” University project (CPU2018GY22) and China Postdoctoral Science Foundation, 2022M713476.
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Data availability: Not applicable.
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