ß-Amyloid-Induced Tau Phosphorylation does not Correlate with Degeneration in Cultured Neurons

Abstract

Treatment of cultured neurons with ß-amyloid (Aß) evokes multiple consequences, including calcium influx, production of reactive oxygen species (ROS), hyperphosphorylation of tau. Which of these events is the major cause of Aß-induced neurodegeneration has been the subject of controversy. We undertook to determine whether or not the accumulation of hyperphosphorylated tau mediated neurodegeneration. Murine cortical neurons demonstrated increased phospho-tau immunoreactivity between 2–8 hr after treatment of murine cortical neurons with Aß_25–35. Cultures underwent overall neurodegeneration between 8–16 hr as ascertained by phase-contrast microscopy, a commercial “live/dead” assay and externalization of phosphatidyl serine. Unexpectedly, however, the healthiest-appearing neurons in Aß–treated cultures contained relatively more phospho-tau immunoreactivity, while obviously degenerating neurons contained less; degenerating neurons often contained less phospho-tau immunoreactivity than did non-Aß-treated control neurons. By contrast, accumulation of reactive oxygen species, previously demonstrated to mediate Aß-induced neurodegeneration, was most prominent within visibly-degenerating neurons. These studies do not address the long-term consequences of PHF formation; however, they indicate that tau hyperphosphorylation, although a consequence of Aß treatment, does not directly contribute to acute degeneration of cultured neurons.