A team of researchers from the University of Cologne has made an important contribution to understanding the role of the tau protein in Alzheimer’s disease.
Using human induced pluripotent stem cells (iPSCs), the international team demonstrated that a specific variant of the tau protein, known as the 1N4R isoform, mediates the harmful effects of protein clumping in human brain cells.
The study was led by Dr. Hans Zempel from the Institute of Human Genetics, who is also a group leader in the Career Advancement Program (CAP) at the Center for Molecular Medicine Cologne (CMMC) 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 (iPSCs) to demonstrate that the 1N4R tau isoform is responsible for the pathological effects on the cell. iPSCs are human stem cells that are generated from other cells. For example, skin cells can be reprogrammed into iPSCs and then transformed into brain cells (neurons). The researchers tested different forms of the tau protein by expressing them specifically in nerve cells. This allowed them 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. By identifying 1N4R tau as a key protein, we have discovered a potential new target for future treatments.”