Apoptosis mediated neurotoxicity induced by chronic application of beta amyloid fragment 25-35.

To investigate whether and how amyloid-beta protein (A beta) 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 A beta (beta 25-35). A single application of this peptide (25-100 microM) was ineffective but when the neuronal cultures were exposed to beta 25-35 (25-100 microM) 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, beta 25-35 showed the intrinsic ability to polymerize into amyloid-like fibrils in vitro. These results confirm the potential pathogenic role of A beta in AD, and indicate that amyloid fibrils may induce neuronal death through a specific programmed process.