Oxidative stress increases levels of endogenous amyloid-β peptides secreted from primary chick brain neurons

Abstract

Oxidative damage is associated with Alzheimer's disease and mild cognitive impairment, but its relationship to the development of neuropathological lesions involving accumulation of amyloid-β (Aβ) peptides and hyperphosphorylated tau protein remains poorly understood. We show that inducing oxidative stress in primary chick brain neurons by exposure to sublethal doses of H2 O2 increases levels of total secreted endogenous Aβ by 2.4-fold after 20 h. This occurs in the absence of changes to intracellular amyloid precursor protein or tau protein levels, while heat-shock protein 90 is elevated 2.5-fold. These results are consistent with the hypothesis that aging-associated oxidative stress contributes to increasing Aβ generation and up-regulation of molecular chaperones in Alzheimer's disease. © 2008 The Authors Journal compilation © 2008 Blackwell Publishing Ltd/The Anatomical Society of Great Britain and Ireland.