Relationship between stress response and mitochondrial respiration in skeletal muscle of apolipoprotein E4 (APOE4) carriers

Expression of the stress‐inducible chaperone protein, heat shock protein 70 (HSP70/72), is elevated in the Alzheimer’s disease (AD) brain. This may result from mitochondrial stress, as AD mitochondria are characterized by reduced complex IV activity and ATP levels. Further, patients with mild cognitive impairment (MCI) have reduced lipid‐stimulated mitochondrial respiration in skeletal muscle, providing evidence that mitochondrial dysfunction occurs peripherally, manifests early in the disease, and is related to lipid metabolism. Interestingly, the primary genetic risk factor for sporadic AD, the apolipoprotein E4 (APOE4) allele, plays an important role in lipid metabolism. The goal of this study was to characterize the skeletal muscle stress response in APOE4 carriers and the relationship with muscle mitochondrial function.