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Distribution, Levels, and Activity of Glycogen Synthase Kinase-3 in the Alzheimer Disease Brain

Jin-Jing Pei MD, MS, Toshihisa Tanaka MD, PhD, Yunn-Chyn Tung MS, Eva Braak PhD, Khalid Iqbal PhD, Inge Grundke-Iqbal PhD
DOI: http://dx.doi.org/10.1097/00005072-199701000-00007 70-78 First published online: 1 January 1997


A number of studies have implicated a proline-directed protein kinase, glycogen synthase kinase-3 (GSK-3) in the hyperphosphorylation of tau in Alzheimer's disease (AD). Toward understanding the role of GSK-3 in the abnormal hyperphosphorylation of tau in AD we have found that GSK-3 is prominently present in neuronal cell bodies and their processes and co-localizes with neurofibrillary changes in AD brain. Furthermore, the levels of GSK-3 as determined by indirect ELISA are ∼50% increased in the postsynaptosomal supernatant from AD brains as compared to the controls. However, no increase in GSK-3 enzyme activity was detected. In AD brain, with its reduced phosphatase activity, even normal levels of GSK-3 activity might be sufficient for the hyperphosphorylation of tau.

Key Words
  • Alzheimer's disease
  • Enzyme-linked immunosorbent assay (ELISA)
  • Immunoblotting
  • Immunocytochemistry
  • Neurofibrillary degeneration
  • Proline-directed protein kinase GSK-3