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A groundbreaking study by neurogeneticists at the University of Florida has identified a novel genetic mutation linked to a significant increase in Alzheimer’s disease risk. The research, published in the Proceedings of the National Academy of Sciences, reveals an unexpected buildup of toxic proteins in the brain, which differs from the well-known amyloid and tau proteins commonly associated with the disease.
Led by Dr. Lien Nguyen and Dr. Laura Ranum, the study examined 80 autopsy brains of Alzheimer’s patients and found that 45 of them contained toxic polyGR proteins—long chains of glycine and arginine amino acids. “While most Alzheimer’s research has focused on amyloid beta and tau, the polyGR proteins we’ve found in Alzheimer’s brains were unexpected and completely different,” said Dr. Ranum, senior author and director of UF’s Center for NeuroGenetics.
A New Genetic Culprit
The researchers developed an advanced genomic screening method to identify the mutation responsible for producing these toxic proteins. Their analysis pinpointed a repeating DNA sequence (GGGAGA) within the CASP8 gene, which appears to double the risk (2.2-fold) of developing late-onset Alzheimer’s in individuals carrying this genetic variation.
Dr. Nguyen, lead author and assistant professor at UF’s College of Medicine, highlighted the broader implications of the discovery. “This study raises the possibility that other yet-to-be-identified mutations contribute to Alzheimer’s. Our method of isolating this repeated expansion mutation opens new opportunities to find additional genetic culprits that may produce similar toxic proteins.”
Implications for Diagnosis and Treatment
The findings open the door for the development of new biomarkers to improve Alzheimer’s diagnosis and treatment strategies. With over 50% of studied Alzheimer’s brains exhibiting this toxic protein buildup, researchers believe they have uncovered a new and prevalent type of pathology in the disease.
The study also suggests that stress may further increase the production of these proteins, potentially exacerbating Alzheimer’s risk. “One thing we’ve learned about these types of proteins is that stress can increase their production,” Dr. Ranum noted. “Future research should explore the impact of stress as a risk factor for Alzheimer’s and other neurodegenerative disorders.”
Collaborative Effort
This multi-institutional study involved experts from the Icahn School of Medicine at Mount Sinai, the University of Minnesota, Massachusetts General Hospital, the University of Washington, Johns Hopkins University, and the University of Pennsylvania. It also included collaboration with the UF Neuromedicine Human Brain and Tissue Bank and other research institutions dedicated to neurodegenerative diseases.
Looking Ahead
As researchers continue to investigate this newly discovered mutation and its role in Alzheimer’s disease, they hope to pave the way for better diagnostic tools and innovative treatments. Understanding how genetic and environmental factors interact in disease progression could be crucial for future breakthroughs in Alzheimer’s research.
Disclaimer: This article is for informational purposes only and does not constitute medical advice. Individuals concerned about Alzheimer’s disease risk should consult healthcare professionals for personalized guidance and genetic counseling.
