Tau protein as a differential biomarker of tauopathies.

ABSTRACT

Microtubule-associated Tau proteins are the basic component of intraneuronal and glial inclusions observed in many neurological disorders, the so-called tauopathies. Many etiological factors, phosphorylation, splicing, and mutations, relate Tau proteins to neurodegeneration. Molecular analysis has revealed that hyperphosphorylation and abnormal phosphorylation might be one of the important events in the process leading to tau intracellular aggregation. Specific set of pathological tau proteins exhibiting a typical biochemical pattern, and a different regional and laminar distribution, could characterize five main classes of tauopathies. A direct correlation has been established between the regional brain distribution of tau pathology and clinical symptoms; for instance progressive involvement of neocortical areas is well correlated to the severity of dementia in Alzheimer's disease, overall suggesting that pathological tau proteins are reliable marker of the neurodegenerative process. Recent discovery of tau gene mutations in frontotemporal dementia with parkinsonism linked to chromosome 17 has reinforced the predominant role attributed to tau proteins in the pathogenesis of neurodegenerative disorders, and underlined the fact that distinct sets of tau isoforms expressed in different neuronal populations could lead to different pathologies. Overall, a better knowledge of the etiological factors responsible for the aggregation of tau proteins in brain diseases is essential for development of future differential diagnosis and therapeutic strategies. They would hopefully find their application against Alzheimer's disease but also in all neurological disorders for which a dysfunction of Tau biology has been identified.