Corticobasal degeneration and progressive supranuclear palsy share a common tau haplotype

Objective: To analyze the association of polymorphisms in the tau gene with pathologically confirmed corticobasal degeneration (CBD). Background: The authors previously described an extended tau haplotype (H1) that covers the human tau gene and is associated with the development of progressive supra nuclear palsy (PSP). The authors now extend this analysis to CBD, a neurode generative condition with clinical and neuropathologic similarities to PSP. Like PSP, CBD is associated with accumulation of aggregates containing the 4-repeat isoforms of tau. Because of difficulty in diagnosis of CBD, the a uthors only analyzed cases with pathologically confirmed CBD. Methods: The authors collected 57 unrelated, neuropathologically confirmed cases of CBD. Tau sequencing in these cases failed to show the presence of pathogenic mu tations. Polymorphisms that spanned the tau gene were analyzed in all CBD c ases and controls. Results: Analyzing tau polymorphisms in CBD cases showed that the frequency of H1 and H1/H1 was significantly increased when analyz ing all cases and when separating by country of origin. H1 frequency in all CBD cases was 0.921, compared with a control frequency of 0.766 (X-2 = 9.1 , P = 0.00255 [1df], OR 3.56 [8.43 > CI 95% > 1.53]). The H1/H1 frequency w as also significantly higher at 0.842 compared with 0.596 in age-matched co ntrols (X-2 = 17.42,p = 0.00016, 2df), OR 3.61 [7.05 > CI 95% > 1.851). Con clusions: The CBD tau association described here suggests that PSP and CBD share a similar cause, although the pathogenic mechanism behind the two dis eases leads to a different clinical and pathologic phenotype.