A research team from the University of Colonia has made a significant advance to understand the role of Tau protein in Alzheimer’s disease. Using humans -induced pluripotent stem cells (IPSC), the international team has been able to demonstrate that a specific form of the Tau protein, known as 1n4R isoform, is responsible for mediating the toxic effects of protein groups on human brain cells.
The study was published in the Alzheimer’s and dementia Magazine under the title “The TAU 1N4R isoform confers vulnerability of the neurons derived from human IPSC MAPP to the amyloid beta and the neuronal dysfunction induced by Tau phosphorylated TAU”. It was directed by Dr. Hans Zempel of the Institute of Human Genetics, who is also a group leader in the Professional Progress Program (CAP) at the Cologne Molecular Medicine Center (CMMC) of the University of Colonia and the University Hospital of Colonia.
If a person suffers from Alzheimer’s disease, certain proteins accumulate in brain cells, forming groups that restrict the function of normal cells or even make the cell die. Dr. Buchholz’s team and Dr. Zempel have used latest generation techniques, such as the edition of Crispr/Cas9 genes and living cells in pluripotent stem cells induced by humans (IPSC) to demonstrate that Tau 1n4R isoform is responsible for pathological effects on the cell. IPSC are human stem cells that are generated from other cells. For example, skin cells can be reprogrammed in IPSC and from there transform into brain cells (neurons). The researchers tested different forms of the Tau protein by expressing them specifically in nerve cells.
In this way, researchers were able to analyze how each protein isoform affects the cell. According to Dr. Sarah Buchholz, first author of the study, “this study represents a significant advance to help us understand the mechanisms of Alzheimer’s disease. By identifying 1n4r Tau as a key protein, we have discovered a new potential objective for future treatments.” The interdisciplinary approach to the study not only helps to better understand Alzheimer’s disease, but also demonstrates the importance of human cell models in neurodegenerative research. More studies are needed to translate the results of this study into the clinical application, in particular to validate the results in adequate animal models and develop specific therapies that intervene in this process.