p38 kinase is activated in the Alzheimer's disease brain

The p38 mitogen-activated protein kinase is a stress-activated enzyme respo nsible for transducing inflammatory signals and initiating apoptosis. In th e Alzheimer's disease (AD) brain, increased levels of phosphorylated (activ e) p38 were detected relative to age-matched normal brain. Intense phospho- p38 immunoreactivity was associated with neuritic plaques, neuropil threads , and neurofibrillary tangle-bearing neurons. The antibody against phosphor ylated p38 recognized many of the same structures as an antibody against ab errantly phosphorylated, paired helical filament (PHF) tau, although PHF-po sitive tau did not cross-react with the phospho-p38 antibody, These finding s suggest a neuroinflammatory mechanism in the AD brain, in which aberrant protein phosphorylation affects signal transduction elements, including the p38 kinase cascade, as well as cytoskeletal components.