PHF‐tau from Alzheimer's brain comprises four species on SDS‐PAGE which can be mimicked by in vitro phosphorylation of human brain tau by glycogen synthase kinase‐3β

Abstract

Extensive in vitro phosphorylation of a purified preparation of control human brain tau consistently produces four rather than, as previously believed, three tau species on SDS‐PAGE. The species thus generated are shifted on SDS‐PAGE to positions that match those of PHF‐tau isolated from Alzheimer's disease brain. A mixture of recombinant human tau isoforms phosphorylated by GSK‐3β gave similar results to those obtained with control human brain tau. In vitro phosphorylation of the individual recombinant isoforms by GSK‐3β showed that the four bands of PHF‐tau are likely to consist of isoforms 3R,0 alone; 4R,0 with 3R,29; 4R,29 with 3R,58 and 4R,58 alone.