APOPTOSIS MEDIATED NEUROTOXICITY INDUCED BY CHRONIC APPLICATION OF BETA-AMYLOID FRAGMENT 25-35

To investigate whether and how amyloid-beta protein (Abeta) is involve d in the neurodegenerative changes characteristic of Alzheimer's disea se (AD), primary hippocampal neurones from foetal rat brain were expos ed acutely and chronically to micromolar concentrations of a synthetic peptide homologous to residues 25-35 of Abeta (beta25-35). A single a pplication of this peptide (25-100 muM) was ineffective but when the n euronal cultures were exposed to beta25-35 (25-100 muM) repeatedly eve ry two days for ten days, cell survival was dramatically reduced. The structural changes and the DNA fragmentation of cells chronically expo sed to the peptide suggested that neuronal death occurred by apoptosis . Furthermore, beta 25-35 showed the intrinsic ability to polymerize i nto amyloid-like fibrils in vitro. These results confirm the potential pathogenic role of Abeta in AD, and indicate that amyloid fibrils may induce neuronal death through a specific programmed process.