β-Amyloid-induced neurotoxicity of a hybrid septal cell line associated with increased tau phosphorylation and expression of β-amyloid precursor protein

Weidong Le, Wen Jie Xie, Rong Kong, Stanley H. Appel

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

Recent evidence suggests that β-amyloid peptide (β-AP) may induce tau protein phosphorylation, resulting in loss of microtubule binding capacity and formation of paired helical filaments. The mechanism by which β-AP increases tau phosphorylation, however, is unclear. Using a hybrid septal cell line, SN56, we demonstrate that aggregated β-AP1-40 treatment caused cell injury. Accompanying the cell injury, the levels of phosphorylated tau as well as total tau were enhanced as detected immunochemically by AT8, PHF-1, Tau-1, and Tau-5 antibodies. Alkaline phosphatase treatment abolished AT8 and PHF-1 immunoreactivity, confirming that the tau phosphorylation sites were at least at Ser(199/202) and Ser(396). In association with the increase in tau phosphorylation, the immunoreactivity of cell-associated and secreted β-amyloid precursor protein (β-APP) was markedly elevated. Application of antisense oligonucleotide to β-APP reduced expression of β-APP and immunoreactivity of phosphorylated tau. Control peptide β-AP1-28 did not produce significant effects on tau phosphorylation, although it slightly increased cell-associated β-APP. These results suggest that βAP1-40-induced tau phosphorylation may be associated with increased β-APP expression in degenerated neurons.

Original languageEnglish (US)
Pages (from-to)978-985
Number of pages8
JournalJournal of Neurochemistry
Volume69
Issue number3
DOIs
StatePublished - Sep 1997

Keywords

  • β-Amyloid
  • β-Amyloid precursor protein
  • Alzheimer's disease
  • Tau phosphorylation

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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