The role of tau in neurodegeneration has been clarified by the identification of genetic mutations in the tau gene in cases with familial frontotemporal dementia and parkinsonism linked to chromosome 17.
Furthermore, we analyzed some markers located in the common region of linkage (D17S800-D17S791), associated with some cases of familial frontotemporal dementia (FTDP-17), and the SNPs rs1816 and rs937 close to the tau gene, to determine their possible association with sporadic PSP.
Frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) is a familial neurological disorder exhibiting autosomal dominant inheritance.
Importantly, the discovery of mutations in the tau gene in familial forms of frontotemporal dementia and of mutations in the alpha-synuclein gene in familial forms of Parkinson's disease has established that dysfunction of tau protein and alpha-synuclein can cause neurodegeneration.
We screened for tau gene mutations among 24 Japanese (6 familial and 18 sporadic cases) and 4 Polish patients with frontotemporal dementia (FTD) using PCR-SSCP analysis followed by DNA sequencing.
The discovery of mutations in the tau gene in familial frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) has provided a direct link between tau dysfunction and dementing disease.
However, since specific polymorphisms and mutations in the tau gene lead to diverse phenotypes, it is plausible that additional genetic or epigenetic factors influence the clinical and pathological manifestations of both familial and sporadic tauopathies.
Recently exonic and intronic mutations in the gene for microtubule-associated protein tau have been discovered in cases of familial frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17).