Selective phosphorylation of adult tau isoforms in mature hippocampal neurons exposed to fibrillar A beta.
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 beta-amyloid. The dystrophy consisted of focal distortions and swellings within the neurites and an altered phosphorylation of the adult tau isoforms. Fibrillar beta-amyloid induced the concomitant activation of MAP kinase and GSK3 beta. The aberrant activation of several signaling pathways may lead to the abnormal phosphorylation of tau and neuritic degeneration.
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Department of Medicine (Division of Neurology), Brigham and Women's Hospital, Boston, Massachusetts, USA. a-ferreira@nwu.edu
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D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007150:Immunohistochemistry; D008854:Microscopy, Electron; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D051381:Rats; D016875:tau Proteins / Q000378:metabolism* / Q000648:ultrastructure
D016229:Amyloid beta-Peptides; D016875:tau Proteins