Impaired mitochondrial dynamics in the blood of patients with Alzheimer’s disease and Lewy body dementia

Abstract Background Mitochondrial dysfunction is an early event in Alzheimer’s disease (AD) physiopathology and may contribute to neuronal loss in several neurodegenerative diseases, such as Lewy body dementia (LBD). The role of mitochondrial dysfunction in AD have been mostly explored in brain post‐mortem tissues. These studies have particularly highlighted abnormal expression levels of mitochondrial fission and fusion protein. The balance between fission and fusion mechanisms is essential to maintain a pool of functional mitochondria inside the cell. Further studies suggest that this dysfunction may also be observed in immune cells, both in the central nervous system as in blood compartment. In this context, we investigate if mitochondrial dysfunction, in particularly, imbalance of mitochondrial fusion and fission could be detected in peripheral blood mononuclear cells (PBMCs) from AD and LBD patients compared to PBMCs from healthy control subjects. Method Our study is a monocentric retrospective study, using blood derived PBMCs from AD, LBD patients and neurological controls followed at the Cognitive Neurology Center (CNC) in Paris. PBMCs were isolated and stored in Lariboisière hospital’s biobank. Mitochondrial protein level were measured using immunoblot technique. Result Our results show a significant alteration of fusion (MFN2 and OPA1) and fission proteins level (FIS1) in PBMCs of AD and LBD patients. Conclusion These new findings pave the way to explore the proteins implicated in mitochondrial homeostasis at peripheral levels, and may provide a new tool to follow the progression of mitochondrial dysfunction in neurodegenerative diseases.