The relationship between mitochondria and α-synuclein - A study of single substantia nigra neurons

Always use the definitive version when citing. Number of characters in the title: 85 Running title: Mitochondria and Lewy body formation. ubiquitin proteasome system. Abstract Objective: Alpha-synuclein protein aggregates and mitochondrial dysfunction have both been described in substantia nigra neurons from patients with idiopathic Parkinson's disease and dementia with Lewy bodies. We explored 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 eight patients with dementia with Lewy bodies, five patients with Parkinson's disease, and eight controls. Protein expression was determined using immunocytochemistry followed by densometric analysis. Subjects: We examined single substantia nigra neurons from five patients with iPD (mean age 81.2 years), eight patients with DLB (mean age 75 years) and eight neurologically and pathologically normal controls (mean age 74.5 years). The control cases showed minimal Lewy body pathology and cell loss. Patients with DLB and iPD fulfilled the clinical and neuropathological criteria for these diseases. Results: Our results show 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. Conclusion: 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.