Nattaporn Pakpian, Kamonrat Phopin, Kuntida Kitidee, Piyarat Govitrapong and Prapimpun Wongchitrat* Pages 616 - 625 ( 10 )
Background: Mitochondrial dysfunction is a pathological feature that manifests early in the brains of patients with Alzheimer’s Disease (AD). The disruption of mitochondrial dynamics contributes to mitochondrial morphological and functional impairments. Our previous study demonstrated that the expression of genes involved in amyloid beta generation was altered in the peripheral blood of AD patients.
Objective: The aim of this study was to further investigate the relative levels of mitochondrial genes involved in mitochondrial dynamics, including mitochondrial fission and fusion, and mitophagy in peripheral blood samples from patients with AD compared to healthy controls.
Methods: The mRNA levels were analyzed by real-time polymerase chain reaction. Gene expression profiles were assessed in relation to cognitive performance.
Results: Significant changes were observed in the mRNA expression levels of fission-related genes; Fission1 (FIS1) levels in AD subjects were significantly higher than those in healthy controls, whereas Dynamin- related protein 1 (DRP1) expression was significantly lower in AD subjects. The levels of the mitophagy-related genes, PTEN-induced kinase 1 (PINK1) and microtubule-associated protein 1 light chain 3 (LC3), were significantly increased in AD subjects and elderly controls compared to healthy young controls. The mRNA levels of Parkin (PARK2) were significantly decreased in AD. Correlations were found between the expression levels of FIS1, DRP1 and PARK2 and cognitive performance scores.
Conclusion: Alterations in mitochondrial dynamics in the blood may reflect impairments in mitochondrial functions in the central and peripheral tissues of AD patients. Mitochondrial fission, together with mitophagy gene profiles, might be potential considerations for the future development of blood-based biomarkers for AD.
Alzheimer's disease, mitochondrial dynamics, mitophagy, FIS1, DRP1, aging.
Center for Research and Innovation, Faculty of Medical Technology, Mahidol University, Salaya, Nakhon Pathom, Center for Research and Innovation, Faculty of Medical Technology, Mahidol University, Salaya, Nakhon Pathom, Center for Research and Innovation, Faculty of Medical Technology, Mahidol University, Salaya, Nakhon Pathom, Chulabhorn Graduate Institute, Chulabhorn Royal Academy, Bangkok, Center for Research and Innovation, Faculty of Medical Technology, Mahidol University, Salaya, Nakhon Pathom