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. 1993 Aug;143(2):565–578.

Biochemical and anatomical redistribution of tau protein in Alzheimer's disease.

E B Mukaetova-Ladinska 1, C R Harrington 1, M Roth 1, C M Wischik 1
PMCID: PMC1887045  PMID: 8342603

Abstract

We have developed assays that distinguish tau protein incorporated into the core structure of the paired helical filament (PHF) from non-PHF tau protein in brain tissue, whether soluble or insoluble. The PHF content was 19-fold greater in Alzheimer's disease cases compared with cognitively intact controls, and in temporal cortex the difference was 40-fold. There was a threefold decrease in soluble tau protein in Alzheimer's disease cases compared with normal age-matched controls, the decrease being greatest in frontal cortex. The PHF content was closely correlated with the number of tau-immunoreactive dystrophic neurites in plaques and throughout the neuropil, whereas counts of neurofibrillary tangles were poorer predictors of PHF content. beta-Amyloid deposits correlated neither with PHF content nor with neurofibrillary pathology. These findings suggest that Alzheimer's disease is characterized by a substantial redistribution of available tau protein from free to PHF-incorporated fractions and that PHF accumulation may be important in neurites as well as tangles in predicting the extent of cognitive impairment in Alzheimer's disease.

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