Which modules of the tau protein, in neurons of Alzheimer disease patients, may act in a destructive manner were investigated by researchers from the Max Planck Institute for Biophysical Chemistry (Göttingen) and the Max Planck Unit for Structural Molecular Biology (Hamburg) with the help of Nuclear Magnetic Resonance Spectroscopy ( PLoS Biology , February 17, 2009).
Coordination becomes difficult, items disappear, keeping new information in the mind is impossible. Worldwide almost 30 million people suffer from Alzheimer's disease, a neurodegenerative, irreversible ailment which starts with memory gaps and ends in helplessness and the loss of personality. The most critical factor in developing Alzheimer's disease is age. Most cases occur after the age of 65.
Two hallmarks are typical for Alzheimer affected brains. One of them, located between nerve cells, is amyloid plaques - extracellular protein aggregates mainly composed of a protein named beta-amyloid. The other clue is intracellular tau fibrils. In the interplay with genetic factors, the latter contribute to a disordered communication within the cell. This triggers cell death.
But the tau protein is not only harmful. Quite the contrary is the case. In its normal non-pathogenic form tau binds to microtubules, long tubular cytoskeletal building blocks, which serve as "tracks" for intracellular transport. In patients afflicted by Alzheimer's disease or similar dementia, tau is abnormally altered. In its pathogenic form tau possesses more phosphorylated amino acids than in its normal healthy counterpart. "Our interest was focussed on how certain phosphorylated residues alter the structure of tau in a way that it can not bind to microtubules anymore" explains Markus Zweckstetter at the Max Planck Institute for Biophysical Chemistry.
Exotic among proteins
Tau is special and with most biophysical methods, such as X-ray crystallography, not analyzable. Neither heat nor acid can harm the protein. Whereas most proteins fold to adopt the structure necessary for their function, tau can do it in the absence of folded structure, is very flexible and changes its form very rapidly.