SYMPATHETIC NEURITE OUTGROWTH IS GREATER ON PLAQUE-POOR VS. PLAQUE-RICH REGIONS OF ALZHEIMERS-DISEASE CRYOSTAT SECTIONS

Senile plaques are a characteristic histopathological feature of Alzhe imer's disease (AD) and are associated with altered neuritic morpholog y. Numerous individual plaque components, most notably beta-amyloid, h ave been studied for their possible effects on neurite outgrowth in cu lture. However, the effect of senile plaques on neuronal morphology an d function is difficult to assess. In the present study, the effect of senile plaques on neurite outgrowth was studied by culturing embryoni c chick sympathetic neuronal explants on Alzheimer's tissue sections. Explants were cultured for 3 days on amygdala tissue sections from AD as well as non-AD patients in serum-free medium. Neurite outgrowth on plaque-rich regions was compared with outgrowth on plaque-poor regions of the same tissue section, and with outgrowth on non-AD tissue, thro ugh colocalization of the living explants and the underlying plaques. Explants growing on plaque-rich regions showed significantly less neur ite outgrowth compared with those on plaque-poor regions in the same s ection or on control brain tissue. These results suggest that plaques are poor substrates for neurite outgrowth as compared with non-plaque areas of the same tissue sections, and support the hypothesis that com ponents of the senile plaques may inhibit neurite outgrowth. (C) 1998 Elsevier Science B.V.