Factors Affecting Pro- and Anti-Oxidant Properties of Fragments of the β-Protein Precursor (βPP): Implication for Alzheimer's Disease

Abstract

Oxidative stress may have a key pathogenetic role in neurodegenerative diseases including Alzheimer's disease (AD). While there is evidence that some amyloid-β (Aβ) peptides can initiate oxidative stress at micromolar doses, there is also some evidence that oxidative stress increases the concentration of the β-protein precursor (βPP) and the potential for increased formation of the Aβ peptides. The following studies were performed to test the hypothesis that fragments of βPP could be antioxidants and hence that oxidative stress might be an early event in AD. We found that several fragments of βPP, including the Aβ peptides, inhibit ascorbate-stimulated lipid peroxidation (ASLP) in membrane fragment preparations of postmortem human brain. In contrast, other fragments of βPP enhance ASLP. These data indicate that βPP or fragments of bPP could play a key role in the redox status of cells and that alterations in bPP processing could have profound effects on the cellular response to oxidative stress.