beta-Amyloid-Induced Tau Phosphorylation does not Correlate with Degeneration in Cultured Neurons.
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.
Ekinci
Fatma J.
FJ
Center for Cellular Neurobiology and Neurodegeneration Research Department of Biological Sciences University of Massachu-setts Lowell, Lowell, MA, USA.
Shea
Thomas B.
TB