Progression patterns of neuronal loss and Lewy body pathology in the substantia nigra in Parkinson's disease

Parkinson's disease (PD) is neuropathologically defined as a disorder with prominent loss of dopaminergic neurons in the substantia nigra (SN) and widespread occurrence of Lewy bodies. In the normal SN, neurons of the medial and dorsal parts are heavily pigmented, followed by the paranigral nucleus, whereas the neurons in the ventrolateral part contain a small amount of melanin. In PD, neuronal loss is most severe in the ventrolateral part. In contrast, neurons in the dorsal part are relatively preserved. Neuronal loss in the medial part and paranigral nucleus is of intermediate severity. Lewy body pathology first occurs in the ventrolateral part, spreads to the paranigral nucleus and then to the medial part, and finally to the dorsal part. These findings suggest that the severity of neuronal loss in the SN is inversely related to the melanin content, and that the progression of Lewy body pathology is parallel to that of neuronal loss.