Deposits of Aβ fibrils are not toxic to cortical and hippocampal neurons in vitro

Amyloid β peptide (Aβ), 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 Aβ. The neurons attached rapidly to A β 1–40 and A β 1–42 substrates and extended long, branching neurites. Quantitative assessment demonstrated that survival of neurons on the Aβ matrices was equivalent to or better than on control substrates of poly L-lysine or poly L-ornithine. In contrast, preparations of Aβ 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 β 1–40 and A β 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 Aβ of senile plaques is not sufficient by itself to cause the plaque-associated neuronal degeneration characteristic of AD.