Relationship between mitochondria and α-synuclein: a study of single substantia nigra neurons.

OBJECTIVE To explore the relationship between α-synuclein pathology and mitochondrial respiratory chain protein levels within single substantia nigra neurons. DESIGN We examined α-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 α-synuclein pathology. However, there are significantly higher levels of the respiratory chain subunits in neurons containing α-synuclein pathology. CONCLUSIONS The finding of increased levels of respiratory chain complex subunits within neurons containing α-synuclein does not support a direct association between mitochondrial respiratory chain dysfunction and the formation of α-synuclein pathology.