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.

journal_name

Neurobiol Aging

journal_title

Neurobiology of aging

authors

Wischik CM,Edwards PC,Lai RY,Gertz HN,Xuereb JH,Paykel ES,Brayne C,Huppert FA,Mukaetova-Ladinska EB,Mena R

doi

10.1016/0197-4580(95)97327-d

subject

Has Abstract,Author List Incomplete

pub_date

1995-05-01 00:00:00

pages

409-17; discussion 418-31

issue

3

eissn

0197-4580

issn

1558-1497

pii

019745809597327D

journal_volume

16

pub_type

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