Apoptosis mediated neurotoxicity induced by chronic application of β amyloid fragment 25–35

Abstract

To investigate whether and how amyloid-β protein (Aβ) is involved in the neurodegenerative changes characteristic of Alzheimer's disease (AD), primary hippocampal neurones from foetal rat brain were exposed acutely and chronically to micromolar concentrations of a synthetic peptide homologous to residues 25–35 of Aβ (β 25–35). A single application of this peptide (25–100 μM) was ineffective but when the neuronal culture were exposed to β 25–35 (25–100 μM) repeatedly every two days for ten days, cell survival was dramatically reduced. The structural changes and the DNA fragmentation of cells chronically exposed to the peptide suggested that neuronal death occurred by apoptosis. Furthermore, β 25–35 showed the intrinsic ability to polymerize into amyloid-like fibrils in vitro. These results confirm the potential pathogenic role of Aβ in AD, and indicate that amyloid fibrils may induce neuronal death through a specific programmed process.