Alzheimer’s disease is the leading cause of dementia in older adults and is driven by a combination of genetic and environmental factors. Many genetic locations have been identified as factors affecting risk, but one major part of the genome has been largely excluded from research: the X chromosome. This chromosome, along with the Y chromosome, determines biological sex and differs between males and females because males have one X chromosome and females have two, one of which is usually inactive. This difference affects how genes are expressed and leads to differences in disease manifestations. By delving into this understudied area, scientists aim to complete a genetic map of Alzheimer’s disease and discover new ways to understand, diagnose and treat the disease.
Researchers led by Dr. Céline Bellenguez of the Institut Pasteur in Lille and colleagues from various European institutions have conducted one of the most detailed investigations into this area. The study, published in Molecular Psychiatry, highlights how certain regions on the X chromosome influence Alzheimer’s risk, providing new insights into this complex disease.
The study involved a very large number of participants, allowing for a thorough examination. “The X chromosome makes up about 5 percent of the human genome, but its role in Alzheimer’s disease has been largely ignored,” said Dr. Bellenguez. mathematical tools for patterns) to explore unique features of the X chromosome, such as how it is expressed differently in males and females. Despite the difficulties, they identified several areas of interest that may be related to Alzheimer’s risk.
Their findings reveal key regions on the X chromosome that may be linked to the likelihood of Alzheimer’s disease. Although they did not find a conclusive genetic risk factor, the study identified important regions in genes such as FMPD4 and DMD, including DNA variants or slight changes. These genes are known to play a role in brain function and cognitive processes involved in thinking, memory and decision-making, which are critical to understanding how neurodegenerative diseases develop. Rare changes in genes such as WNK3 and DACH2 were also noted, emphasizing the need for more research in these areas.
The team emphasized the study’s significance because of its careful approach. Unlike earlier genetic studies, which often excluded the X chromosome due to its complex nature, this work incorporates it and uses specialized methods that specifically target the X chromosome’s unique biological design method to address its unique characteristics. This represents a step forward in understanding the complete genetic landscape of Alzheimer’s disease.
Dr. Berengues’ team believes these findings may lead to better ways to diagnose and treat Alzheimer’s disease. They emphasize the importance of conducting larger, more detailed studies to further investigate the genetic structure of the X chromosome. As Dr. Bellenguez explains, “This study marks the beginning of new research on how the X chromosome affects the development of Alzheimer’s disease and the differences between men and women.” The different ways in which Alzheimer’s disease manifests in men and women may spark a broader discussion about the importance of personalized medicine and treatments that target individual genetic and biological differences.
The work also sheds light on why women are more susceptible to Alzheimer’s, a disparity that has puzzled researchers for decades. By examining the genetic contributions associated with the X chromosome, the study not only reveals new areas of research but also raises hope for the development of more effective diagnostic tools and therapeutic strategies to address this imbalance.
The findings encourage scientists to rethink long-held views about Alzheimer’s disease and its causes. By incorporating the The revelation of the potential role of the X chromosome provides a sense of discovery and innovation, highlighting the importance of integrating previously overlooked aspects into Alzheimer’s research.
Journal reference
Le Borgne J., Gomez L., Heikkinen S., Amin N., Ahmad S., Choi SH, et al. “X-chromosome-wide association study in Alzheimer’s disease.” Molecular Psychiatry, 2024.
About the author
Dr. Celine Berengues He is a well-known researcher in the field of neurogenetics, focusing on uncovering the genetic mechanisms of Alzheimer’s disease and related neurodegenerative diseases. Based in Europe, she explores how genetic variation affects disease susceptibility, aiming to bridge the gap between basic genetics and clinical applications.
Dr. Bellenguez’s research is characterized by the innovative use of large-scale genetic studies, including genome-wide association studies, to identify key genetic loci associated with disease processes. Her work often emphasizes the importance of incorporating neglected genomic regions, such as the X chromosome, to more fully understand complex diseases.
Dr. Bellenguez is a respected figure in the field, working with international research teams to push the boundaries of Alzheimer’s research. Her contributions have paved the way for potential advances in diagnostic tools and personalized treatment strategies, bringing hope to the millions of people living with neurodegenerative diseases.
