Mitochondrial Dysregulation in Skeletal Muscle from Patients Diagnosed with Alzheimer’s Disease and Sporadic Inclusion Body Myositis

Abstract

Mitochondrial dysfunction is implicated in Alzheimer’s disease (AD) anddisruption of mitochondrial dynamic pathways has been documented in brains frompatients diagnosed with AD; although it is unclear whether other tissues arealso affected. Much less is known about the mitochondria in patients diagnosedwith sporadic Inclusion Body Myositis (sIBM). The current study examinedmitochondrial biology in skeletal muscle from AD and sIBM patients compared tohealthy, elderly individuals. Skeletal muscle samples were obtained from theNational Disease Research Interchange and mRNA, protein content, and enzymeactivity was used to assess mitochondrial parameters. Patients diagnosed withAD or sIBM demonstrated reduced mitofusin 2 and optic atrophy protein 1protein. AD patients also displayed increased mRNA of superoxide dismutase 2,catalase, and uncoupling protein 3. Amyloid b precursor protein mRNA was higher in sIBMpatients only compared to both AD patients and elderly individuals. Both totaland phosphorylated AMPK protein content, an upstream regulator of mitochondrialdynamics and biogenesis, were also reduced in sIBM patients. The current studydemonstrates a disruption in signaling pathways regulating mitochondrialdynamics in both AD and sIBM patients, although the underlying causes maydiffer.