The tau gene A0 polymorphism in progressive supranuclear palsy and related neurodegenerative diseases
- aNeurogenetics Section, University Department of Clinical Neurology, bParkinson’s Disease Society Brain Research Centre, cDementia Research Group, Institute of Neurology, Queen Square, London, UK, dNational Hospital for Neurology and Neurosurgery, Queen Square, London, UK
- Dr NW Wood, Neurogenetics Section, University Department of Clinical Neurology, Institute of Neurology, Queen Square, London WC1N 3BG, UK. Telephone 0044 171 837 3611; fax 0044 171 278 5616; email n.wood{at}ion.ucl.ac.uk
- Received 9 July 1998
- Revised 2 November 1998
- Accepted 10 November 1998
Abstract
Progressive supranuclear palsy is characterised pathologically by the deposition of neurofibrillary tangles consisting of tau protein. Patients with the disease have been reported to have a more frequent occurrence of one allele of an intronic polymorphism of thetau gene. Other diseases which may involve tau deposition include frontotemporal dementia and corticobasal degeneration. This polymorphism has been studied in a series of subjects with progressive supranuclear palsy, corticobasal degeneration, frontotemporal dementia, idiopathic Parkinson’s disease, and normal controls to (1) confirm this association in a large series and (2) to investigate a possible role for this association in other disorders which involve tau deposition. The results confirm the finding of an overrepresentation of the A0 allele and the A0/A0 genotype in patients with progressive supranuclear palsy, in the largest series reported to date. The A0 allele was found in 91% of patients with progressive supranuclear palsy as opposed to 73% of controls (p<0.001) and the A0/A0 genotype was seen in 84% of patients as compared with 53% of controls (p<0.01). There was no significant difference between patients with Parkinson’s disease, frontotemporal dementia, or corticobasal degeneration, and controls. The A0 allele may have a direct effect on tau isoform expression in progressive supranuclear palsy or it may be in linkage disequilibrium with an adjacent determinant of tau gene expression. The explanation for this difference between a predisposition factor to progressive supranuclear palsy and the other conditions may lie in the molecular pathology of these diseases.
