Wk. Liu et al., Relationship of the extended tau haplotype to tau biochemistry and neuropathology in progressive supranuclear palsy, ANN NEUROL, 50(4), 2001, pp. 494-502
Two extended haplotypes of the tau gene (H1 and H2) have been described. Th
e frequency of H1 haplotype is increased in progressive supranuclear palsy
(PSP). PSP is associated with filamentous tau lesions in neurons and glia,
which are reportedly composed exclusively of tau isoforms with four repeats
in the microtubule-binding domain (4R tau). To determine the influence of
the tau haplotype on tau isoform composition and neuropathology, we studied
25 PSP cases and 6 Alzheimer's disease patients matched for age, sex, and
postmortem delay. In the basal ganglia, tau and amyloid burdens were determ
ined to see if there was an effect of concurrent Alzheimer-type pathology,
and the ratio of 4R to 3R tau was measured in detergent-insoluble tau fract
ions. Insoluble tau from PSP was not composed exclusively of 4R tau. All br
ains had a mixture of 4R and 3R tau, but the ratio was different in Alzheim
er's disease and PSP. In Alzheimer's disease there was less 4R than 3R tau,
whereas the ratio was reversed in PSP. In PSP cases with concurrent Alzhei
mer-type pathology, the ratio of 4R to 3R was intermediate between Alzheime
r's disease and PSP. The H1 haplotype had no effect on the 4R to 3R ratio o
r on tau and amyloid burdens. In summary, the H1 haplotype does not have a
major influence on the pathological or biochemical phenotype of PSP.