Eva-Maria and Eckhard Mandelkow have with their team achieved significant progress in Alzheimer's research in the course of their studies of a protein called "Tau". It is the basic substance of so-called neurofibrillary tangles (NFTs) - tiny protein deposits that accumulate in the brains of Alzheimer's patients. In the normal state, tau binds the cytoskeleton of neurons, in particular, it stabilizes the transport routes, along which their substances are transported within cells. Very early in Alzheimer's disease, the tau protein however changes, detaches itself from the cytoskeleton and agglomerates. Since the 1990s, Eva-Maria and Eckhard Mandelkow have analyzed this protein. Longtime, the importance of the tau protein in Alzheimer’s disease has been underestimated. “At that time, no one would have thought that tau has such a significant role. However, we have pursued this approach because we have been interested in the role of Tau in nerve cells“ said Eva-Maria Mandelkow.
In pioneering studies, she and her husband have shown why the tau protein lumps in the brain and which sections of the molecular structure are thereby decisive. These findings allowed the couple to examine the consequences of the aggregation of the tau protein for the nerve cells in more detail. The result: Modifications of normal tau destroy the synapses of nerve cells. This is for example shown by studies on mice. If the protein accumulates in nerve cells, these mice perform worse in learning and memory tests than healthy animals and develop typical symptoms of Alzheimer's disease. In the event that the production of the toxic tau in the cells is stopped, the synapses regenerate and the mice recover from amnesia. This observation shows that the disease process is in principle reversible.
Eckhard Mandelkow: "I am of the opinion that an effective therapy against Alzheimer is possible. Crucial, in my view, is that the treatment is started early enough. Many of today's therapy approaches might have failed on account of the fact that they are applied too late. Since a disease is usually only diagnosed when typical symptoms such as memory dysfunctions are evident. At this time, the brain is however already severely damaged."
Recently, the couple has examined 200,000 substances, in order to find an active agent against the aggregation of tau. Some of these substances were found to be potential candidates for drugs. Their effect will now be further explored.
Prof. Dr. Eckhard Mandelkow studied physics and did his PhD at the Max Planck Institute for Medical Research in Heidelberg on the structure of virus proteins. In a subsequent research period at the Brandeis University (USA), he already dealt with proteins of the cytoskeleton and then continued this line of research. Then he focused on the structure and function of proteins of the nerve cells, especially of motor proteins, tau proteins and their pathological changes during the neurodegeneration. He is the head of the working group "Structural principles of neurodegeneration" at the DZNE/caesar in Bonn.
Dr. Eva-Maria Mandelkow studied medicine, worked for several years in the clinic and then pursued a career in fundamental research. She received her PhD at the Max Planck Institute for Medical Research in Heidelberg for her work in muscle physiology. This was followed by research periods at the Brandeis University (USA), the Scripps Research Institute (USA) and at the MRC Laboratory in Cambridge (UK), where she dealt with proteins of the cytoskeleton. Eva-Maria Mandelkow heads the working group "Cell and animal models of neurodegeneration" at the DZNE/caesar in Bonn.
