Biological sex is one of the strongest known factors influencing Alzheimer’s disease risk, with women nearly twice as likely as men to develop the condition. However, the biological reasons behind this difference are not yet fully understood.

Researchers at the University of Miami Miller School of Medicine are now investigating whether part of the explanation may lie in the X chromosome. Supported by a new award from the National Institute on Aging, part of the NIH, the research team will examine how genetic and epigenetic changes on the X chromosome may contribute to Alzheimer’s disease risk and help explain differences between women and men.

Although the X chromosome represents nearly 5% of the human genome and contains hundreds of protein-coding genes, it has often been overlooked in large genetic studies because of its complex biology. Women typically have two X chromosomes, while men have one. In females, one X chromosome is largely inactivated to balance gene activity, although some genes can escape this process, resulting in complex differences in gene expression.

The researchers will analyze large and diverse datasets to identify X chromosome variations associated with Alzheimer’s disease. They will also study DNA methylation and other molecular changes that may influence how genes are regulated, particularly during aging—the strongest known risk factor for Alzheimer’s disease.

By combining genetic, epigenetic and molecular data, the team hopes to uncover previously overlooked biological pathways and better understand how X chromosome variations may affect brain health and disease risk. The findings could also support more accurate risk prediction and help advance precision approaches to Alzheimer’s prevention and treatment.

The project addresses an important gap in Alzheimer’s research, as much of the disease’s inherited risk remains unexplained and the X chromosome has frequently been excluded from major genomic studies. Researchers hope that a deeper understanding of its role could reveal new risk factors, potential therapeutic targets and important insights into why Alzheimer’s disease affects women and men differently.

Source: https://news.med.miami.edu/x-chromosome-alzheimers-risk-women-study/