AMYLOID-BETA PROTEIN-INDUCED NEURONAL CELL-DEATH - NEUROTOXIC PROPERTIES OF AGGREGATED AMYLOID-BETA PROTEIN

The neurotoxic effects of soluble and aggregated synthetic amyloid bet a protein (AbetaP) have been investigated in rat primary cultures. Fre shly solubilized beta(1-40) was neurotoxic not to immature, but to mat ure hippocampal neurons. On the other hand, aggregated beta(1-40) was neurotoxic to both. Neurotoxicity induced by aggregated beta(1-40) was 10-fold more potent than soluble beta(1-40) and was not prevented by substance P. The neurotoxicity of aggregated beta(1-40) to cultured ne urons depended on the peptide concentration and the duration of exposu re to, it. Cerebral cortical and hippocampal neurons were significantl y susceptible to aggregated beta(1-40) than cerebellar granular cells, and cultured astrocytes were not vulnerable to aggregated beta(1-40) even at high concentrations.