However, Braak PD Stages 1 and 2, occur ‘before’ Lewy body pathology occurs in the substantia nigra, and in those stages there are already reduced neuronal densities of tyrosine hydroxylase (TH) positive neurons and a higher percentage of TH-immunonegative melanin-laden neurons.4 This suggests that neurodegeneration and neuronal dysfunction precede alpha-synuclein (α-syn) positive Lewy pathology in the substantia nigra. The gene discussed is SNCA; the disease is Parkinson disease.