Tau is a
microtubule-associated protein mainly expressed in neurons of central nervous system, which is crucial in the maintenance of these cells. It has a central role in the polymerization and stabilization of microtubules and in the traffic of organelles along axons and dendrites. Aggregates of hyperphosphorylated forms of
tau protein participate in the formation of neurofibrillary tangles, which characterize numerous
neurodegenerative disorders named
tauopathies. The analysis of tau gene and the study of familial cases of
tauopathies have led to the discovery of tau gene mutations that cause inherited
dementia designated as
Frontotemporal dementia (FTD) with
parkinsonism linked to chromosome 17 (FTDP-17). However, these familial cases remain rare compared to the sporadic
tauopathies, the later involving both genetic and environmental etiologic factors. As tau pathology represents a primary pathogenic event in various
neurodegenerative diseases, the hypothesis that tau genotype could influence the development of these diseases was tested by several groups. This review summarizes advances in the molecular genetics of the tau gene, as well as recent studies addressing the disease incidence of novel tau polymorphisms in different
neurodegenerative diseases. Hopefully, the identification of several genetic defects of the tau gene will be helpful in improving our understanding of the role of
tau protein in the pathogenesis of various
neurodegenerative diseases.