Sympathetic neurite outgrowth is greater on plaque-poor vs. plaque-rich regions of Alzheimer's disease cryostat sections.

ABSTRACT

Senile plaques are a characteristic histopathological feature of Alzheimer's disease (AD) and are associated with altered neuritic morphology. Numerous individual plaque components, most notably beta-amyloid, have been studied for their possible effects on neurite outgrowth in culture. However, the effect of senile plaques on neuronal morphology and function is difficult to assess. In the present study, the effect of senile plaques on neurite outgrowth was studied by culturing embryonic 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, through colocalization of the living explants and the underlying plaques. Explants growing on plaque-rich regions showed significantly less neurite outgrowth compared with those on plaque-poor regions in the same section 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 components of the senile plaques may inhibit neurite outgrowth.