The tau gene A0 allele and progressive supranuclear palsy

Background: Recent studies have shown an association between a polymorphic tandem repeat allele, located in intron 9, of the tau gene and progressive supranuclear palsy (PSP). Objective: To investigate this tan polymorphism i n individuals with a clinical diagnosis of sporadic or familial PSP as well as in cases confirmed by pathology. Methods: We analyzed the frequency of tau intronic polymorphism, the presence of linkage in two families with mul tiple cases of PSP, the splicing of exon 10, and direct sequence of the tal c gene. Results: We found that patients with a clinical diagnosis of sporad ic or familial PSP and individuals with PSP confirmed by neuropathology hav e greater prevalence of the AO allele and A0/A0 genotype than controls. Thi s finding, however, was also true for asymptomatic relatives of individuals with PSP. Linkage analysis in familial PSP excluded the location of the ge ne in the region 17q21. Furthermore, no significant differences were found in the level of expression of exon 10 in PSP, A0/A0 brain with respect to A lzheimer A3/A3 brain. We found no mutations in the tau gene in individuals with familial PSP. Conclusions: A mutation in the talc gene was not the pri mary cause of familial PSP. The role of tau and the talc AO allele in white PSP patients remains unknown, although it may represent a genetic risk fac tor for several neurodegenerative disorders.