Activation of caspase-3 corresponds to severity of PD. Immunodetection of active caspase-3 in TH-immunoreactive dopamine neurons in the SN of AMC (A-C), prePD (D-F), and PD (G-I) patients. In an AMC case (A), arrow identifies a dopamine neuron immunopositive for active caspase-3 in an area otherwise containing little active caspase-3. In addition, depicted are magnified views of subcellular localization of active caspase-3 in reference to the nuclei (B, E, H) as well as of individual neurons in merged images (C, F, I). Panel (I), contains an additional inset at the magnification of the main panel (I) illustrating vividly the boundaries of the DAPI-positive nucleus within a TH-immunoreactive dopamine neuron to more clearly depict the extent of active caspase-3 labelling within the nucleus. Scale bar equals 50 μm (A, D, and G) or 18 μm (B, C, E, F, H, I, and inset in I). Asterisks in (C, F, and I) identify neuromelanin.