Glycogen Synthase Kinase 3 Alteration in Alzheimer Disease Is Related to Neurofibrillary Tangle Formation

Highly phosphorylated τ protein is the main component of paired helical filaments (PHF), which comprise the neurofibrillary tangles (NFT) in some neurons of patients with Alzheimer disease (AD). Glycogen synthase kinase 3 (GSK3) phosphorylates τ in vitro at several sites also found to be phosphorylated in PHF-τ, τ is phosphorylated at these sites in both AD and normal control (NC) brains, although the extent of phosphorylation is far greater in τ from AD. If GSK3 levels are increased in AD, then τ phosphorylation and perhaps PHF formation may occur. To quantify GSK3, blots of AD and NC brain supernatant and particulate fractions were probed with antibodies to GSK3. In particulate fractions of AD compared to NC, GSK3α immunoreactivity did not increase, but in fact, decreased 40%, and GSK3β immunoreactivity decreased 30%. GSK3α and GSK3β levels correlated well with each other. GSK3 levels correlated negatively with numbers of NFT.