ELECTROCHEMICAL ANALYSIS OF PROTEIN NITROTYROSINE AND DITYROSINE IN THE ALZHEIMER BRAIN INDICATES REGION-SPECIFIC ACCUMULATION

HPLC with electrochemical array detection (HPLC-ECD) was used to quant ify 3,3'-dityrosine (diTyr) and 3-nitrotyrosine (3-NO2-Tyr) in four re gions of the human brain that are differentially affected in Alzheimer 's disease (AD). DiTyr and 3-NO2-Tyr levels were elevated consistently in the hippocampus and neocortical regions of the AD brain and in ven tricular cerebrospinal fluid (VF), reaching quantities five- to eightf old greater than mean concentrations in brain and VF of cognitively no rmal subjects. Uric acid, a proposed peroxynitrite scavenger, was decr eased globally in the AD brain and VF. The results suggest that AD pat hogenesis may involve the activation of oxidant-producing inflammatory enzyme systems, including nitric oxide synthase.