GLYCOGEN-SYNTHASE KINASE-3 INDUCES ALZHEIMERS DISEASE-LIKE PHOSPHORYLATION OF TAU - GENERATION OF PAIRED HELICAL FILAMENT EPITOPES AND NEURONAL LOCALIZATION OF THE KINASE

Glycogen synthase kinase-3 (GSK-3) reduced the mobility of human tau on SDS-PAGE, prevented binding of the monoclonal antibody (mAb). Tau.l, and induced binding of the mAb 8D8. Recombinant tau phosphorylated by GSK-3 aligned on SDS-PAGE with the abnormally phosphorylated tau (PHF-tau) associated with the paired helical filaments in Alzheimer's disease brain. Phosphorylated serine396 (numbering of the largest human brain tau isoform) was identified as a binding site on tau for mAb 8D8. The localisation of GSK-3 within granular structures in pyramidal cells indicates that GSK-3alpha and GSK-3beta may have a role in the production of PHF-tau in Alzheimer's disease.