Relationship of the extended tau haplotype to tau biochemistry and neuropathology in progressive supranuclear palsy

Citation
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
Citations number
37
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurology,"Neurosciences & Behavoir
Journal title
ANNALS OF NEUROLOGY
ISSN journal
0364-5134 → ACNP
Volume
50
Issue
4
Year of publication
2001
Pages
494 - 502
Database
ISI
SICI code
0364-5134(200110)50:4<494:ROTETH>2.0.ZU;2-W
Abstract
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.