How senile plaques and neurofibrillary tangles are linked represents a major gap in our understanding of the pathophysiology of Alzheimer's disease. We characterized a hippocampal neuronal culture system in which tau undergoes maturation in vivo; rat neurons maintained in culture for more than 3 weeks replicated the splicing and phosphorylation changes that tau undergoes upon maturation in situ. Using this model system, we induced an Alzheimer-like neuritic dystrophy following the application of fibrillar β-amyloid. The dystrophy consisted of focal distortions and swellings within the neurites and an altered phosphorylation of the adult tau isoforms. Fibrillar β- amyloid induced the concomitant activation of MAP kinase and GSK3 β. The aberrant activation of several signaling pathways may lead to the abnormal phosphorylation of tau and neuritic degeneration.
ASJC Scopus subject areas
- Molecular Biology
- Cellular and Molecular Neuroscience
- Cell Biology