Treatment of cultured neurons with beta-amyloid (Abeta) evokes multiple 
consequences, including calcium influx, production of reactive oxygen species 
(ROS), hyperphosphorylation of tau. Which of these events is the major cause of 
Abeta-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 Abeta_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 Abeta-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-Abeta-treated control neurons. By contrast, accumulation of 
reactive oxygen species, previously demonstrated to mediate Abeta-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 Abeta 
treatment, does not directly contribute to acute degeneration of cultured 
neurons.