Contribution of somal Lewy bodies to neuronal death

Neuronal degeneration occurs in the substantia nigra pars compacta (SNpc) of patients with Parkinson's disease and other Lewy body-associated disorders. Lewy bodies (LBs) are abnormal inclusions found in the SNpc and other neurons of these patients. It is not known what role LBs play in the disease process; they may be harmful to the neuron or simply an epiphenomenon of the disease process. We have previously shown that some of the neuronal death occurring in the SNpc of Lewy body-associated disorders resembles apoptosis. The present study was undertaken to determine whether apoptotic-like changes were more common in SNpc neurons with somal LBs compared to those without somal LBs. Substantia nigra from cases of Lewy body-associated disorders were labeled to colocalize apoptotic-like changes and LBs using in situ end-labeling and an anti-ubiquitin antibody. Three cases demonstrated that SNpc neurons with LBs in the perikarya had the same proportion of apoptotic-like changes as SNpc neurons without somal LBs. One case had no LB-containing SNpc neurons undergoing apoptotic-like cell death. The majority of SNpc neurons undergoing apoptotic-like cell death did not appear to contain somal LBs and thus may be dying before LB formation can occur. These results support the theory that the presence of a somal LB does not predispose a neuron to undergo apoptotic-like cell death.