Dual Roles Of Amyloid-Beta And Secreted Forms Of Amyloid Precursor Protein In Culture

摘要

We studied the effects of various gene products of human amyloid precursor protein (APP), secreted APP, and amyloid beta protein (Abeta) in rat cortical, hippocampal, and PC12 cell cultures. Our results showed 1) Adenoviral-mediated APP gene transfer significantly increased APP levels and cell death in cortical neuronal cultures, supporting the notion that over-expression of APP causes neuronal death. 2) Cultures treated with sAPPa exhibited more neurite outgrowth and cell viability, while depletion of endogenous APP by antisense decreased neurite outgrowth from differentiated PC 12 cells, indicating neurotrophic effects. 3) Abeta_(25-35) caused significant hippocampal neuron death while Abeta_(1-42) partially prevented differentiated PC 12 cell death in the presence of high concentrations of calcium, suggesting the dual effects of Abeta peptide. Our findings suggest that distinct dual roles of Abeta and secreted forms of APP relating to neuronal viability are implicated in the pathogenesis of AD.