Mitochondrial Alzheimer’s Risk Factors Control APOE Expression and Secretion

The APOE4 gene is the main genetic risk factor for Alzheimer’s disease. The number of copies of this gene in the human genome determines the severity of disease. Therefore, knowledge of how cells control the production of apolipoprotein E (APOE) is necessary to manage APOE4’s deleterious effects on Alzheimer’s disease. We discovered a novel cellular process that, when disrupted, increases cell production of APOE up to 49-fold. This process is the respiration carried out by the metabolic hub of the cell, the mitochondrion, a cellular structure that controls processes ranging from cell death to aging. Defective mitochondria and APOE4 strongly associate to Alzheimer’s—but the cause and effect remain unknown. Our results show that a mitochondrial defect can augment the expression of APOE. Thus, we postulate mitochondria could modify disease severity and its progression rate.