Relationship Between Mitochondria and α-Synuclein A Study of Single Substantia Nigra Neurons

Objective: To explore the relationship between alpha-synuclein pathology and mitochondrial respiratory chain protein levels within single substantia nigra neurons. Design: We examined alpha-synuclein and mitochondrial protein expression in substantia nigra neurons of 8 patients with dementia with Lewy bodies, 5 patients with Parkinson disease, and 8 control subjects. Protein expression was determined using immunocytochemistry followed by densometric analysis. Patients: We examined single substantia nigra neurons from 5 patients with idiopathic Parkinson disease (mean age, 81.2 years), 8 patients with dementia with Lewy bodies (mean age, 75 years), and 8 neurologically and pathologically normal control subjects (mean age, 74.5 years). The control cases showed minimal Lewy body pathology and cell loss. Patients with dementia with Lewy bodies and idiopathic Parkinson disease fulfilled the clinical and neuropathologic criteria for these diseases. Results: Our results showed that mitochondrial density is the same in nigral neurons with and without alpha-synuclein pathology. However, there are significantly higher levels of the respiratory chain subunits in neurons containing alpha-synuclein pathology. Conclusions: The finding of increased levels of respiratory chain complex subunits within neurons containing alpha-synuclein does not support a direct association between mitochondrial respiratory chain dysfunction and the formation of alpha-synuclein pathology.