TAU PROTEIN AND HUMAN TAUOPATHIES: AN OVERWIEV*

Abstract

The growing knowledge of the molecular mechanisms of neurodegenerative diseases isunveiling 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 largegroup of neurodegenerative diseases, mostly dementias, these diseases have been collectively called tauopathies. In the healthy adult brain, tau protein is found in six isoformsthat contain either three or four microtubule-binding domains, which divides them in twogroups, 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 forthe classification of tauopathies into five classes, according to the tau isoforms compositionand structure of filaments. The filaments aggregate intracellularly, forming the so-calledfibrillary tau inclusions (FTI).Today, the accurate diagnosis of tauopathies is possible only post mortem, when the spreadof FTI across the brain is observed. The form and distribution of FTI differs among thediseases. They are detected by several neuropathological techniques, which differ in theirefficacy to label tangles from different diseases. The causes for this differential labelling arestill not understood.There is no cure for tauopathies, but better efficacy of some drugs that may slow down thecognitive decline in the early stages of the diseases and the need for monitoring the drugeffects are calling for early pre mortem diagnostic tools. New imaging techiques employingmolecular labels for pathological tau aggregates promise to provide a sensitive diagnostictool. In order to make it sufficiently specific, differential binding characteristics of molecular imaging probes to different forms of pathological tau should be carefully assessed andconsidered in developing imaging techniques for diagnosing tauopathies in vivo.