Scientists have long struggled to understand what causes most cases of Alzheimer’s disease. While researchers have focused on amyloid beta and tau proteins, new findings suggest that another type of protein buildup may also play a major role.
A team of neurogeneticists at the University of Florida has identified a new genetic mutation linked to Alzheimer’s. Their research, led by Dr. Lien Nguyen and Dr. Laura Ranum, found that more than half of the Alzheimer’s patients they studied had a buildup of toxic proteins called polyGR—something completely different from amyloid and tau.
This discovery could open new possibilities for diagnosing and treating the disease. The findings were published in the Proceedings of the National Academy of Sciences.
A Surprising Discovery in the Brain
The researchers studied 80 autopsy brains from Alzheimer’s patients and found that 45 of them (more than 50%)contained toxic clumps of polyGR proteins. Until now, these proteins were not known to be associated with Alzheimer’s.
Unlike amyloid and tau, which have been the main focus of Alzheimer’s research, polyGR proteins come from a different genetic process. They form when a section of DNA with repeating sequences produces proteins that harm brain cells.
To identify the source of this protein buildup, the researchers searched for a genetic mutation responsible for making polyGR.
A New Genetic Risk Factor for Alzheimer’s
The team developed a high-tech method to scan the entire human genome of patients and pinpoint repeated DNA segments that could produce polyGR. They found that a specific DNA repeat sequence—GGGAGA (pronounced “GEE-GEE Gaga”)—in a gene called CASP8 was linked to the disease.
People who carry a certain variation of this repeated DNA sequence have more than double the risk (2.2 times higher)of developing late-onset Alzheimer’s disease. This discovery suggests that genetic factors beyond amyloid and tau may significantly contribute to the disease.
What This Means for Alzheimer’s Research
According to Dr. Nguyen, the lead author of the study, this discovery is just the beginning. The method used to find this repeat expansion mutation could help scientists uncover even more hidden genetic factors that might be contributing to Alzheimer’s and other neurodegenerative diseases.
These results could also lead to the development of new biomarkers—biological indicators that could improve early diagnosis of Alzheimer’s. Additionally, researchers may be able to design new therapies that target these toxic proteins, offering potential new treatment options.
Could Stress Make Alzheimer’s Worse?
The study also raises questions about how stress interacts with this genetic mutation. Dr. Ranum, a leading expert in repeat expansion disorders, noted that stress has been shown to increase the production of these toxic proteins in other diseases.
This suggests that people who carry the CASP8 mutation may be even more vulnerable to Alzheimer’s if they experience chronic stress.
Understanding how stress affects these proteins could lead to new prevention strategies for people at risk of developing Alzheimer’s. Future research will need to explore whether reducing stress can slow down or prevent the buildup of polyGR proteins in the brain.
A Collaborative Effort
This groundbreaking study involved scientists from multiple institutions, including Mount Sinai, the University of Minnesota, Massachusetts General Hospital, the University of Washington, Johns Hopkins University, and the University of Pennsylvania. It also relied on brain tissue from the UF Neuromedicine Human Brain and Tissue Bankand other national research centers.
The Future of Alzheimer’s Research
With over 50% of Alzheimer’s patients showing this newly identified protein buildup, researchers believe they have unlocked a new direction for studying the disease. The discovery of polyGR proteins and their connection to a specific genetic mutation could change the way scientists understand, diagnose, and eventually treat Alzheimer’s.
While much more research is needed, these findings represent a major step forward in solving the mystery of what causes Alzheimer’s and how to stop it.
If you care about brain health, please read studies about vitamin D deficiency linked to Alzheimer’s and vascular dementia, and blood pressure problem at night may increase Alzheimer’s risk.
For more information about brain health, please see recent studies about antioxidants that could help reduce dementia risk, and epilepsy drug may help treat Alzheimer’s disease.
The research findings can be found in PNAS.
Copyright © 2025 Knowridge Science Report. All rights reserved.
