A research team at the University of Cologne has made a significant breakthrough in understanding the role of the tau protein in Alzheimer's disease.
University of CologneFeb 28 2025 A research team at the University of Cologne has made a significant breakthrough in understanding the role of the tau protein in Alzheimer's disease. Using human induced pluripotent stem cells , the international team has been able to show that a specific form of the tau protein , known as the 1N4R isoform, is responsible for mediating the toxic effects of protein clumps in human brain cells.
The study was published in the Alzheimer's & Dementia journal under the title "The TAU isoform 1N4R confers vulnerability of MAPT knockout human iPSC-derived neurons to amyloid beta and phosphorylated TAU-induced neuronal dysfunction". It was led by Dr Hans Zempel from the Institute of Human Genetics, who is also a group leader in the Career Advancement Program at the Center for Molecular Medicine Cologne of the University of Cologne and University Hospital Cologne.
If a person suffers from Alzheimer's disease, certain proteins accumulate in brain cells, forming clumps that restrict normal cell function or even cause the cell to die. Dr Buchholz and Dr Zempel's team have used state-of-the-art techniques such as CRISPR/Cas9 gene editing and live-cell imaging in human induced pluripotent stem cells to demonstrate that the 1N4R tau isoform is responsible for the pathological effects on the cell.
Related StoriesThe researchers tested different forms of the tau protein by expressing them specifically in nerve cells. In this way, the researchers were able to analyse how each protein isoform affects the cell. According to Dr. Sarah Buchholz, first author of the study, "this study represents a significant advance in helping us to understand the mechanisms of Alzheimer's disease.
Alzheimer's Disease Brain Cell Dementia Induced Pluripotent Stem Cells Knockout Neurons Research Stem Cells Tau Protein
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