Intermediates involved in serotonin oxidation catalyzed by Cu bound Aβ peptides

The degradation of neurotransmitters is a hallmark feature of Alzheimer's disease (AD). Copper bound Aβ peptides, invoked to be involved in the pathology of AD, are found to catalyze the oxidation of serotonin (5-HT) by H 2 O 2 . A combination of EPR and resonance Raman spectroscopy reveals the formation of a Cu( ii )-OOH species and a dimeric, EPR silent, Cu 2 O 2 bis-μ-oxo species under the reaction conditions. The Cu( ii )-OOH species, which can be selectively formed in the presence of excess H 2 O 2 , is the reactive intermediate responsible for 5-HT oxidation. H 2 O 2 produced by the reaction of O 2 with reduced Cu( i )-Aβ species can also oxidize 5-HT. Both these pathways are physiologically relevant and may be involved in the observed decay of neurotransmitters as observed in AD patients. The mononuclear copper hydroperoxo species (Cu( ii )-OOH) of Cu-Aβ is the active oxidant responsible for serotonin oxidation by Cu-Aβ in the presence of physiologically relevant oxidants like O 2 and H 2 O 2 , which can potentially cause oxidative degradation of neurotransmitters, a marker of Alzheimer's disease.