Aβ(25-35) peptide displays H₂O₂-like reactivity towards aqueous FE²⁺, nitroxide spin probes, Ant) synaptosomal membrane proteins

Amyloid beta peptides (Aβs) are found in abnormally high accumulations in brains of persons with Alzheimer's disease, and are believed to contribute to cognitive decline in this disorder. Synthetic Aβ and its peptide fragment 25-35 [Aβ(25-35)] are toxic to cells in culture; however, the exact mechanism of amyloid peptide toxicity is not known. An emerging hypothesis contends that Aβ toxicity results from peptide-mediated free radical reactions and generation of reactive oxygen species [Hensley, et al., Proc. Natl. Acad. Sci. USA 19: 3270-3274 (1994); Harris, et al., Exp. Neurol. 131: 193-202 (1995)]. Recently, we reported that reactivity of Aβ toward the oxidation-sensitive enzyme glutamine synthetase is related to the peptide's reactivity toward the spin trap phenyl-tert-butyl nitrone (PBN) [Hensley, et al., Neuroreport 6: 489-492 (1995)]. Neuronal damage may be due, in part, to oxidative processes initiated by amyloid-derived free radicals species. This work presents evidence from electron paramagnetic resonance (EPR) spin labeling techniques and spectrophotometric assays that a portion of synthetic Aβ(25-35) demonstrates hydrogen peroxide-like reactivity toward Fe²⁺, nitroxide spin probes, and neocortical synaptasomal membrane proteins. These results are discussed with reference to free radical membrane damage and neurotoxicity in Alzheimer's disease.