Neuronal death in lewy body disease

Abstract

In Parkinson's disease and other Lewy body-associated disorders, neurons in the substantia nigra pars compacta (SNpc) undergo degeneration, but the mechanism of cell death has not been previously described. The substantia nigra of normal and Alzheimer's disease cases were compared with substantia nigra from patients with Lewy bodyassociated disorders (Parkinson's disease, concomitant Alzheimer's/Parkinson's disease, and diffuse Lewy body disease) using in situ end-labeling to detect fragmented DNA. In situ end-labeled neurons demonstrated changes resembling apoptosis: nuclear condensation, chromatin fragmentation and formation of apoptotic-like bodies. Ultrastructural analysis confirmed nuclear condensation and formation of apoptotic-like bodies. Apoptotic-like changes were seen in the substantia nigra of both normal and disea·sed cases; concomitant Alzheimer's/Parkinson's disease and diffuse Lewy body disease cases had significantly higher amounts of apoptotic-like changes than normal controls or Alzheimer patients. Parkinson's disease cases were not significantly different from controls, probably due to high variation among cases of Parkinson's disease. Control and Alzheimer's disease patients had the same percentage of apoptotic-Iike changes. Lewy bodies (LBs) are abnormal inclusions found in the SNpc neurons of patients with Lewy body-associated disorders. It is not known what role LBs play in the disease process. We sought to discover whether apoptotic-like changes were more common in SNpc neurons with or without somal· LBs. In SNpc tissue from cases with Lewy body-associated disorders, .cells were double-labeled to colocalize apoptotic-like changes and LBs with in 'Situ .endlabeling and anti-ubiquitin antibody. Nigral neurons with LBs showed the same amount of apoptotic-like changes as nigral neurons without LBs. The majority of SNpc neurons undergoing apoptotic-like cell death did not appear to contain somal LBs. These results support the theory that the presence of a somal LB does not predispose a neuron to undergo apoptoticlike cell death.