This pathology-associated decline in AT1 and the accompanying increase in Nox4 from AMC to prePD and finally to PD is suggestive of a progressive loss of dopamine neurons in nigral matrix and nigrosome 1 due to excess Nox4 generation in the nucleus of dopamine neurons and a consequent increase in production of superoxide at levels that precipitate nucleic acid damage leading to neuronal dysfunction and death. This evidence concerns the gene NOX4 and Parkinson disease.