Glycogen synthase kinase-3 induces Alzheimer's disease-like phosphorylation of tau: generation of paired helical filament epitopes and neuronal localisation of the kinase

Neurosci Lett. 1992 Nov 23;147(1):58-62. doi: 10.1016/0304-3940(92)90774-2.


Glycogen synthase kinase-3 (GSK-3) reduced the mobility of human tau on SDS-PAGE, prevented binding of the monoclonal antibody (mAb), Tau.1, 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-3 alpha and GSK-3 beta may have a role in the production of PHF-tau in Alzheimer's disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / metabolism*
  • Blotting, Western
  • Brain Chemistry
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Electrophoresis, Polyacrylamide Gel
  • Glycogen Synthase Kinases
  • Hippocampus / metabolism
  • Humans
  • Intermediate Filaments / enzymology*
  • Neurons / enzymology*
  • Phosphorylation
  • Protein Kinases / metabolism*
  • Recombinant Proteins / metabolism
  • tau Proteins / metabolism*


  • Recombinant Proteins
  • tau Proteins
  • Protein Kinases
  • Glycogen Synthase Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases