Two-dimensional characterization of paired helical filament-tau from Alzheimer’s disease: demonstration of an additional 74-kDa component and age-related biochemical modifications

Abstract: PHF-tau proteins are the major components of the paired helical filament (PHF) from Alzheimer‘s disease (AD) neurofibrillary lesions. They differ both qualitatively and quantitatively in their degree of phosphorylation when compared with native tau proteins. However, little is known about the extent and heterogeneity of phos-phorylated sites or the isoform composition and the iso-electric variants of PHF-tau. Therefore, we have charac-terized PHF-tau proteins from cortical brain tissue ho-mogenates of 13 AD patients using two-dimensional gel electrophoresis. Whatever the topographical origin of brain tissue homogenates, PHF-tau proteins shared the same two-dimensional gel electrophoresis profile made of a tau triplet of 55, 64, and 69 kDa. A 74-kDa hyperphos-phorylated tau component was detected particularly i