DISTRIBUTION, LEVELS, AND ACTIVITY OF GLYCOGEN-SYNTHASE KINASE-3 IN THE ALZHEIMER-DISEASE BRAIN

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 i n the abnormal hyperphosphorylation of tau in AD we have found that GS K-3 is prominently present in neuronal cell bodies and their processes and co-localizes with neurofibrillary changes in AD brain. Furthermor e, the levels of GSK-3 as determined by indirect ELISA are similar to 50% increased in the postsynaptosomal supernatant from AD brains as co mpared 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 hyperphos phorylation of tau.