Alzheimer's disease: Researchers discover role of key protein

Using human induced pluripotent stem cells (iPSCs), a research team at the University of Cologne in Germany 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, published in the Alzheimer’s & Dementia journal, 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 from there transformed into brain cells (neurons).

The 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, 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,” Buchholz noted.

The study’s interdisciplinary approach not only helps to better understand Alzheimer’s disease but also demonstrates the importance of human cell models in neurodegenerative research.

—IANS