The tau gene A0 polymorphism in progressive supranuclear palsy and relatedneurodegenerative diseases

Progressive supranuclear palsy is characterised pathologically by the depos ition of neurofibrillary tangles consisting of tau protein. Patients with t he disease have been reported to have a more frequent occurrence of one all ele of an intronic polymorphism of the tall gene. Other diseases which may involve tau deposition include frontotemporal dementia and corticobasal deg eneration. This polymorphism has been studied in a series of subjects with progressive supranuclear palsy corticobasal degeneration, frontotemporal de mentia, idiopathic Parkinson's disease, and normal controls to (1) confirm this association in a large series and (2) to investigate a possible role f or this association in other disorders which involve tau deposition. The re sults confirm the finding of an overrepresentation of the A(0) allele and t he A(0)/A(0) genotype in patients with progressive supranuclear palsy, in t he largest series reported to date. The A(0) allele was found in 91% of pat ients with progressive supranuclear palsy as opposed to 73% of controls (p< 0.001) and the A(0)/A(0) genotype was seen in 84% of patients as compared w ith 53% of controls (p<0.01). There was no significant difference between p atients with Parkinson's disease, frontotemporal dementia, or corticobasal degeneration, and controls. The A(0) allele may have a direct effect on tau isoform expression in progressive supranuclear palsy or it may be in linka ge disequilibrium with an adjacent determinant of tau gene expression. The explanation for this difference between a predisposition factor to progress ive supranuclear palsy and the other conditions may lie in the molecular pa thology of these diseases.