TAU PROTEIN AND HUMAN TAUOPATHIES: AN OVERWIEV

The growing knowledge of the molecular mechanisms of neurodegenerative diseases is unveiling their common characteristics, enabling their classification according to the pathologically changed protein that aggregates in the diseased central nervous system. Due to aggregation of hyperphosphorilated microtubule associated protein tau in a large group of neurodegenerative diseases, mostly dementias, these diseases have been collectively called tauopathies. In the healthy adult brain, tau protein is found in six isoforms that contain either three or four microtubule-binding domains, which divides them in two groups, accordingly. In the pathological tau filaments, all six isoforms can be found, although their representation in the filaments varies among the diseases, as does the structure of the filaments, which can be paired helical, straight or random coiled. This allows for the classification of tauopathies into five classes, according to the tau isoforms composition and structure of filaments. The filaments aggregate intracellularly, forming the so-called fibrillary tau inclusions (FTI). Today, the accurate diagnosis of tauopathies is possible only post mortem, when the spread of FTI across the brain is observed. The form and distribution of FTI differs among the diseases. They are detected by several neuropathological techniques, which differ in their efficacy to label tangles from different diseases. The causes for this differential labelling are still not understood. There is no cure for tauopathies, but better efficacy of some drugs that may slow down the cognitive decline in the early stages of the diseases and the need for monitoring the drug effects are calling for early pre mortem diagnostic tools. New imaging techiques employing molecular labels for pathological tau aggregates promise to provide a sensitive diagnostic tool. In order to make it sufficiently specific, differential binding characteristics of molecular imaging probes to different forms of pathological tau should be carefully assessed and considered in developing imaging techniques for diagnosing tauopathies in vivo.