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 Alzheimerʹs 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 Aβ1–40 and Aβ1–42 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 Aβ1–40 and Aβ1–42 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.