The significance of the amyloid plaque core proteins (APCP) in Alzheimer's disease (AD) and its consequences for neuronal survival have been controversial. To address this problem we purified the APCP and beta A obtained from brains with AD, and assessed their biological effects in tissue culture. APCP and beta A caused severe toxicity to chick and rat sympathetic and sensory neurons whose survival is dependent upon NGF. This toxicity was dose dependent and reversible at low doses. APCP and beta A prevented sprouting of neurites in freshly plated neurons. In established cultures addition of these molecules caused vacuolation and fragmentation of neurites and disintegration of neuronal soma. We suggest that the deposition of APCP in AD may be partly responsible for the destruction of the neuritic arbor, thereby contributing to the formation of the neuritic plaque and to neuronal death.