Increased tau phosphorylation at the Ser396 epitope after amyloid beta-exposure in organotypic cultures.
The hallmarks of Alzheimer's disease include extracellular plaques primarily consisting of amyloid-beta peptide and intracellular neurofibrillary tangles composed of highly phosphorylated tau protein. We report that exposure of organotypic hippocampal cultures to synthetic amyloid-beta peptide(25-35) (50 microM, 96 h) causes neurodegeneration concomitant with a significant increase in tau phosphorylation at the Ser epitope (+60%). Furthermore, the level of active glycogen synthase kinase-3beta (GSK-3beta [pTyr]) was increased (+55%) after amyloid-beta peptide(25-35) exposure. These findings support the role of amyloid-beta peptide as a mediator of tau phosphorylation and demonstrate the usefulness of organotypic cultures for investigating the link between amyloid-beta peptide-induced neurotoxicity and tau phosphorylation. Our results also confirm that amyloid-beta peptide induces activation of glycogen synthase kinase-3beta.
Johansson
Sara
S
Local Discovery Research Area CNS & Pain Control, AstraZeneca, Södertälje, Sweden.
Jämsä
Anne
A
Vasänge
Mervi
M
Winblad
Bengt
B
Luthman
Johan
J
Cowburn
Richard F
RF
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western / Q000379:methods; D000939:Epitopes / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D009924:Organ Culture Techniques / Q000379:methods; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012694:Serine / Q000378:metabolism*; D013997:Time Factors; D016875:tau Proteins / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D000939:Epitopes; D016875:tau Proteins; D012694:Serine