Research ArticleAlzheimer’s Disease

A second X chromosome contributes to resilience in a mouse model of Alzheimer’s disease

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Science Translational Medicine  26 Aug 2020:
Vol. 12, Issue 558, eaaz5677
DOI: 10.1126/scitranslmed.aaz5677

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The advantage of an extra X

Whether sex chromosomes contribute to sex difference in Alzheimer’s disease (AD) is unknown. In AD, men die earlier, whereas women live longer. During aging and preclinical AD, men show more cognitive deficits than do women. Davis et al. now report that the X chromosome may affect AD-related vulnerability in a mouse model of AD. Engineering mice to harbor a second X chromosome conferred resilience in male and female mice, in part through Kdm6a, an X chromosome gene that escapes inactivation. In humans, variation in the KDM6A gene was associated with higher expression in the brain and less cognitive decline. These results imply that having a second X chromosome could contribute to counteracting AD vulnerability.

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