DEPOSITS OF A-BETA FIBRILS ARE NOT TOXIC TO CORTICAL AND HIPPOCAMPAL-NEURONS IN-VITRO

Amyloid beta peptide (A,beta), which is deposited as insoluble fibrils in senile plaques, is thought to play a role in the neuropathology of Alzheimer's disease. We have developed a model in which rat embryonic cerebral cortical or hippocampal neurons are seeded onto culture dish es containing deposits of substrate-bound, fibrillar A beta. The neuro ns attached rapidly to A beta(1-40) and A beta(1-42) substrates and ex tended long, branching neurites. Quantitative assessment demonstrated that survival of neurons on the A beta matrices was equivalent to or b etter than on control substrates of poly L-lysine or poly L-ornithine. In contrast, preparations of A beta fibrils added directly to the cul ture medium caused neuronal death as previously reported in the litera ture. These results reveal that the response of neurons to deposited A beta(1-40) and A beta(1-42) is substantially different from that obse rved with suspensions of the amyloid peptides, with the former serving as growth-promoting substrates for cortical and hippocampal neurons. This may thus imply that fibrillar A beta of senile plaques is not suf ficient by itself to cause the plaque-associated neuronal degeneration characteristic of AD.