2-DIMENSIONAL CHARACTERIZATION OF PAIRED HELICAL FILAMENT-TAU FROM ALZHEIMERS-DISEASE - DEMONSTRATION OF AN ADDITIONAL 74-KDA COMPONENT ANDAGE-RELATED BIOCHEMICAL MODIFICATIONS

PHF-tau proteins are the major components of the paired helical filame nt(PHF) from Alzheimer's disease (AD) neurofibrillary lesions. They di ffer both qualitatively and quantitatively in their degree of phosphor ylation when compared with native tau proteins. However, little is kno wn about the extent and heterogeneity of phosphorylated sites or the i soform composition and the isoelectric variants of PHF-tau. Therefore, we have characterized PHF-tau proteins from cortical brain tissue hom ogenates 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 hyperphosphoryla ted tau component was detected particularly in the youngest and most s everely affected AD patients. This additional component of hyperphosph orylated tau was shown to correspond to the longest brain tau isoform. Furthermore, the isoelectric points of PHF-tau from older AD patients were significantly more basic, indicating a lower degree of phosphory lation. These results show that the severity of neurofibrillary degene ration of AD is modulated by age.