Here, we report that dopamine neurons from intact substantia nigra of neurologically and neuropathologically normal patients (AMC) differ substantially with respect to the levels of AT1 expression as well as intranuclear expression of superoxide-generating Nox4, nuclear oxidative stress, and cellular activation of caspase-3 from clinically asymptomatic patients, who had only modest dopamine cell loss, but had Braak stages that were consistent with a neuropathological diagnosis of PD (referred to here as prePD), and from advanced PD patients. Here, NOX4 is linked to Parkinson disease.