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.