The fundamental causes of most forms of Alzheimer’s disease remain a mystery. Now, researchers have revealed a new piece of puzzle.
The neurogenetists of the University of Florida led by Lien Nguyen, Ph.D. and Laura Ranum, Ph.D., have discovered a new genetic mutation and an associated accumulation of toxic proteins in the brain, a different type of accumulation of amyloid or Tau, proteins that have long been the focus of Alzheimer’s research .
Unexpectedly, the researchers found that 45 of 80 autopsy brains of patients with Alzheimer’s showed the accumulation of toxic proteins containing long chains of amino acids glycine and arginine (Polygr). The findings were reported today in the newspaper. Proceedings of the National Academy of Sciences.
“While the majority of Alzheimer’s research has focused on the accumulation of Beta and Tau Amiloid, the polygr proteins we have found in Alzheimer’s brains were unexpected and completely different,” said Ranum, author and senior director of the study of the study of the study of the study of the study of the study of the study of UF neurogenetic center.
This new discovery led researchers to look for a “guilty”, a genetic mutation that could produce these proteins.
In the article, the researchers describe how they developed a high technology form to quickly classify the complete human genome of a patient and take a repetitive segment of DNA with a repetition of GGGAGA (pronounced “Gee-Gee Gaga”) that produces toxic polygic proteins . According to the findings, the people who carry a specific variation of this repeated DNA chain, which resides in a gene called CASP8, have more than double the risk (2.2 times) to develop late start Alzheimer’s.
“This study also raises the possibility that other unidentified mutations contribute to those of Alzheimer’s,” said Nguyen, principal author of the study and assistant professor in the Department of Molecular Genetics and Microbiology of the UF Faculty of Medicine in the UF in the UF. “The method used to isolate this repeated expansion mutation opens new opportunities to find other genetic culprits that can produce similar toxic proteins.”
In the future, these results could be used to develop new biomarkers that can lead to a better diagnosis and the development of new therapeutic approaches to go to these toxic proteins.
“With more than 50% of the positive Alzheimer’s brains for this accumulation of toxic proteins,” said Nguyen, “we believe we have identified a new and frequent type of pathology new addresses for Alzheimer’s research.”
In addition, according to the research team, the findings support the investigation of whether a combination of genetic mutation and stress further increases the risk of Alzheimer’s.
“One thing we have learned about this type of protein in their study during the last 15 years is that stress can increase its production,” said Ranum, a distinguished professor in the Molecular Genetics and Microbiology Department whose work specializes in repeated expansion mutations. and its role in neurodegenerative disorders. “The impact of various types of stress as a risk factor for Alzheimer’s and a complete class of repeated expansion disorders will be important for future studies.”
Nguyen and Ranum directed a team of multiple institutions that included researchers at the ICAHN School of Medicine in Mount Sinai, the University of Minnesota, the Massachusetts General Hospital, the University of Washington, the Johns Hopkins University and the University of Pennsylvania. The study also involved collaboration with the Bank of Tisos and Berbro of UF neuromedicine tisos, the national centralized repository for Alzheimer’s disease and related dementia, and the Institute of Neurodegenerative Disease at the Massachusetts General Hospital.
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