Supercomplex formation of mitochondrial respiratory chain complexes in leukocytes from patients with neurodegenerative diseases

With population aging, cognitive impairments and movement disorders due to neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD) and dementia with Lewy bodies (DLB), are increasingly considered as key social issues. Clinically, it has remained challenging to diagnose them before the onset of symptoms because of difficulty to observe the progressive loss of neurons in the brain. Therefore, with exploratory research into biomarkers, a number of candidates have previously been proposed, such as activities of mitochondrial respiratory chain complexes in blood in AD and PD. In this study, we focused on the formation of mitochondrial respiratory chain supercomplexes (SCs) because the formation of SC itself modulates the activity of each complex. Here we investigated the SC formation in leukocytes from patients with AD, PD and DLB. Our results showed that SCs were well formed in AD and PD compared with controls, while poorly formed in DLB. We highlighted that the disruption of the SC formation correlated with the progression of PD and DLB. Taking our findings together, we propose that pronounced SC formation would already have occurred before the onset of AD, PD and DLB and, with the progression of neurodegeneration, the SC formation would gradually be disrupted. Graphical Abstract