Genetic variation at the tau locus and clinical syndromes associated with progressive supranuclear palsy

A number of different clinical syndromes have been associated with progressive supranuclear (PSP) tau pathology. Previous reports have suggested that atypical clinical phenotypes of PSP occur in familial disease, and might be associated with mutations of MAPT. We examined the association of PSP-susceptibility tau haplotypes in pathologically diagnosed PSP, separated according to initial clinical features into classic PSP and atypical PSP groups (PSP-Parkinsonism, PSP-P). These patients were screened for mutations in exons 1 and 10 of MAPT. No mutations were found in 75 patients (21 PSP-P), and H1c was associated with both Richardson's syndrome and PSP-P compared with controls. Routine screening for MAPT mutations in atypical PSP is not recommended.