In Alzheimer's disease, certain proteins build up in brain cells, forming clumps that disrupt normal function and may even cause cell death.
A research team from the University of Cologne has made a significant breakthrough in understanding the role of the tau protein in Alzheimer's. Using human induced pluripotent stem cells (iPSCs), the international team identified a specific variant of the tau protein—the 1N4R isoform—as a key factor in the harmful effects of protein clumping in brain cells.
The study, led by Dr. Hans Zempel from the Institute of Human Genetics, involved advanced techniques such as CRISPR/Cas9 gene editing and live-cell imaging.
Dr. Zempel, who is also a group leader in the Career Advancement Program (CAP) at the Center for Molecular Medicine Cologne (CMMC), collaborated with Dr. Sarah Buchholz and their team to investigate how different forms of tau affect nerve cells.
iPSCs, which are derived from reprogrammed human cells such as skin cells, can be transformed into neurons for research. By selectively expressing various tau protein isoforms in these nerve cells, the researchers were able to analyze their impact. Their findings confirmed that the 1N4R tau isoform plays a central role in the disease’s progression.
"This study marks a crucial step toward understanding Alzheimer's mechanisms," said Dr. Buchholz, first author of the study. "By identifying 1N4R tau as a key protein, we have uncovered a potential target for future treatments."
The study highlights the importance of human cell models in neurodegenerative research and underscores the need for further studies. Future research will focus on validating these findings in animal models and developing targeted therapies to intervene in the disease process.
Courtesy: ANI
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