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 dishes containing deposits of substrate-bound, fibrillar A beta. The neurons attached rapidly to A beta 1-40 and A beta 1-42 substrates and extended long, branching neurites. Quantitative assessment demonstrated that survival of neurons on the A beta matrices was equivalent to or better than on control substrates of poly L-lysine or poly L-ornithine. In contrast, preparations of A beta fibrils added directly to the culture medium caused neuronal death as previously reported in the literature. These results reveal that the response of neurons to deposited A beta 1-40 and A beta 1-42 is substantially different from that observed 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 sufficient by itself to cause the plaque-associated neuronal degeneration characteristic of AD.