Glycogen synthase kinase 3 alpha and 3 beta do not colocalize with neurofibrillary tangles

Glycogen synthase kinase (GSK) 3 alpha and 3 beta are two proline-directed serine/ threonine kinases that have been shown in vitro to hyperphosphorylate tau, and therefore, may contribute to neurofibillary tangle (NFT) formation in Alzheimer's disease (AD). We report here that, in the human hippocampal formation of both control and AD individuals, GSK 3 alpha and 3 beta are immunohistochemically localized to neurons within the presubiculum > CA1, CA3, and CA4 subfields of the hippocampus, layers III > II > IV, V, VI of entorhinal cortex, and occasional neurons in layers III, V, and VI of temporal neocortex. By contrast, NFTs occur primarily in CA1. subiculum, layers II and IV of entorhinal cortex, and layers II, III, and V of temporal neocortex. The presubiculum and other subfields are frequently spared. Thus, localization of GSK 3 alpha and GSK 3 beta does not correspond to the expected pattern of neuronal vulnerability to NFT formation in AD. Interpreted within the limitations of immunohistochemical detection, these results argue against a major role of GSK 3 alpha or GSK 3 beta in NFT formation in AD.