Neurofibrillary tangle-associated alteration of stathmin in Alzheimerʹs disease

Stathmin (p19), a 19-kDa cytosolic phosphoprotein, plays a key role in converting extracellular signals into intracellular biochemical changes. Antibodies and cDNA specific for stathmin were used to study its levels and localization in normal and Alzheimerʹs disease (AD) brain tissue. The stathmin protein concentration was reduced in AD neocortex as assessed by Western blotting, whereas the concentration of its mRNA detected by both in situ hybridization and slot blot were increased in AD. The alteration of the stathmin protein concentration was negatively correlated with neurofibrillary tangle numbers but not with plaque. Immunoreactivity was evenly localized to the cytoplasm of neurons in control cortical sections, whereas in AD it was preferentially localized to some of the neurofibrillary tangle-bearing neurons. Numbers of stathmin-positive neurons were inversely correlated with tangle numbers but not with plaque numbers in the frontal cortex of AD patients.