Background: Progressive supranuclear palsy (PSP) is a clinicopathological syndrome related to tau deposits and in linkage disequilibrium with tau polymorphisms. Some rare familial PSP cases have been related to tau gene mutations.
Objective: To present the clinical, pathological, and molecular data of one family with early-onset autosomal dominant PSP.
Design: We performed clinical examinations, quantitative neurological tests, positron emission tomographic scans with fluorodopa F 18 and raclopride C 11, analysis of tau mutations, neuropathological examinations, and protein analyses on brain specimens.
Results: Three family members had PSP confirmed by pathological features in the proband. A novel mutation of tau, G303V, was found in the proband and other family members. tau Isoforms with 4 microtubule-binding repeats were overexpressed in the proband brain.
Conclusions: The G303V mutation of tau is associated with autosomal dominant PSP. Expression of 4 microtubule-binding repeat tau isoforms is increased in the proband.