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

Wan Kyng Liu, Tien V. Le, Jennifer Adamson, Matthew Baker, Natalie Cookson, John Hardy, Michael Hutton, Shu Hui Yen, Dennis W Dickson

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Abstract

Two extended haplotypes of the tau gene (H1 and H2) have been described. The 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 determined 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 fractions. Insoluble tau from PSP was not composed exclusively of 4R tau. All brains had a mixture of 4R and 3R tau, but the ratio was different in Alzheimer'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 Alzheimer-type pathology, the ratio of 4R to 3R was intermediate between Alzheimer's disease and PSP. The H1 haplotype had no effect on the 4R to 3R ratio or on tau and amyloid burdens. In summary, the H1 haplotype does not have a major influence on the pathological or biochemical phenotype of PSP.

Original languageEnglish (US)
Pages (from-to)494-502
Number of pages9
JournalAnnals of Neurology
Volume50
Issue number4
DOIs
StatePublished - 2001

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Progressive Supranuclear Palsy
Biochemistry
Haplotypes
Alzheimer Disease
Amyloid
Protein Isoforms
Pathology
Neuropathology
Basal Ganglia
Microtubules
Neuroglia
Detergents
Phenotype
Neurons

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Relationship of the extended tau haplotype to tau biochemistry and neuropathology in progressive supranuclear palsy. / Liu, Wan Kyng; Le, Tien V.; Adamson, Jennifer; Baker, Matthew; Cookson, Natalie; Hardy, John; Hutton, Michael; Yen, Shu Hui; Dickson, Dennis W.

In: Annals of Neurology, Vol. 50, No. 4, 2001, p. 494-502.

Research output: Contribution to journalArticle

Liu, WK, Le, TV, Adamson, J, Baker, M, Cookson, N, Hardy, J, Hutton, M, Yen, SH & Dickson, DW 2001, 'Relationship of the extended tau haplotype to tau biochemistry and neuropathology in progressive supranuclear palsy', Annals of Neurology, vol. 50, no. 4, pp. 494-502. https://doi.org/10.1002/ana.1159
Liu, Wan Kyng ; Le, Tien V. ; Adamson, Jennifer ; Baker, Matthew ; Cookson, Natalie ; Hardy, John ; Hutton, Michael ; Yen, Shu Hui ; Dickson, Dennis W. / Relationship of the extended tau haplotype to tau biochemistry and neuropathology in progressive supranuclear palsy. In: Annals of Neurology. 2001 ; Vol. 50, No. 4. pp. 494-502.
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