Abnormal levels of prohibitin and ATP synthase in the substantia nigra and frontal cortex in Parkinson's disease

Prohibitin and ATP synthase protein levels were examined in the substantia nigra and frontal cortex (area 8) in five cases of Parkinson's disease (PD), five cases of dementia with Lewy bodies pure form (pDLB), five cases of early Alzheimer's disease (AD stage IIA, B), nine cases with advanced AD (stages V/VIC), and nine controls. A significant reduction of prohibitin and ATP synthase was observed in the substantia nigra in PD cases. In contrast, increased prohibitin and ATP synthase levels were found in the frontal cortex in PD, and increased prohibitin but not ATP synthase in the frontal cortex in pDLB. Superoxide dismutase 2 (SOD2) expression levels were also increased in the frontal cortex in PD and pDLB. No modifications in prohibitin and ATP synthase levels were found in the frontal cortex in sporadic AD. These findings demonstrate disease-specific modifications in the expression of mitochondrial-related proteins in the frontal cortex at stages of PD in which there is no α-synuclein aggregation in the form of Lewy bodies and Lewy neurites in this area. These findings emphasize the presence of mitochondrial modifications before the appearance of histological hallmarks of PD, and point to the possibility of a more extended molecular pathology in PD than currently accepted.