title: Quantitative analysis of tau protein in paired helical filament preparations: implications for the role of tau protein phosphorylation in PHF assembly in Alzheimer's disease.
abstract: In Alzheimer's disease, there is a major redistribution of the tau protein pool from soluble to PHF-bound forms. PHF-bound tau can be distinguished from normal tau by acid reversible occlusion of a generic tau epitope in the tandem repeat region and characteristic sedimentation in the if-II protocol developed in this laboratory. We show that 85% of tau bound in the PHF-like configuration can be recovered in the if-II PHF-fraction. Less than 1% of this material was phosphorylated at the mAb AT8 site in aged clinical controls or in cases with minimal or mild dementia. Of tau phosphorylated at the mAb AT8 site, only 12% was found to co-sediment with PHFs. These low levels could not be explained by postmortem dephosphorylation. As more than 95% of PHF-tau is not phosphorylated, even at early stages of pathology, it is misleading to use the terms "PHF-tau" and "phosphorylated tau" as though they were synonymous, particularly as this implies a pathogenetic role which phosphorylation need not have.
authors.affiliation: Cambridge Brain Bank Laboratory, Department of Psychiatry, United Kingdom.
authors.forename: C M
authors.initials: CM
authors.lastname: Wischik
authors.forename: P C
authors.initials: PC
authors.lastname: Edwards
authors.forename: R Y
authors.initials: RY
authors.lastname: Lai
authors.forename: H N
authors.initials: HN
authors.lastname: Gertz
authors.forename: J H
authors.initials: JH
authors.lastname: Xuereb
authors.forename: E S
authors.initials: ES
authors.lastname: Paykel
authors.forename: C
authors.initials: C
authors.lastname: Brayne
authors.forename: F A
authors.initials: FA
authors.lastname: Huppert
authors.forename: E B
authors.initials: EB
authors.lastname: Mukaetova-Ladinska
authors.forename: R
authors.initials: R
authors.lastname: Mena
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D000911:Antibodies, Monoclonal; D001923:Brain Chemistry; D000939:Epitopes; D006801:Humans; D007150:Immunohistochemistry; D009454:Neurofibrils / Q000737:chemistry*; D010766:Phosphorylation; D014461:Ultracentrifugation; D016875:tau Proteins / Q000032:analysis* / Q000502:physiology
chemical_list: D000911:Antibodies, Monoclonal; D000939:Epitopes; D016875:tau Proteins