Blood Bioenergetic Biomarkers in Alzheimer’s Disease APOE ε4-Carriers

Background:This study examined the impact of APOE ε4 on blood cell bioenergetics. Prior studies have shown systemic alterations in blood cells from APOE ε4 carriers.Methods:Platelet mitochondria cytochrome oxidase (COX) and citrate synthase (CS) Vmax activities were measured in APOE ε4 carrier and non-carrier Alzheimer’s disease (AD) subjects, and lymphocyte mitochondria and bioenergetics-relevant protein and viability endpoints were measured using fresh and expanded cultures. Statistical analysis was completed using Student’s T-Test.Results:The mean platelet COX Vmax activity, normalized to protein content, was lower in APOE ε4 carriers and lymphocyte Annexin V, a marker of apoptosis, was significantly higher. PINK1, a protein involved in mitophagy, was higher in APOE ε4 carrier lymphocytes. mTOR and SIRT1, which play a role in energy sensing, were different between the groups; mTOR phosphorylation decreased while SIRT1 phosphorylation increased in APOE ε4 carrier lymphocytes. The lipid synthesis pathway differed, as AceCSI and ATP CL increased in APOE ε4 carrier lymphocytes, and ACC phosphorylation also increased.Conclusions:These findings overall support a relationship between APOE genotype and bioenergetic pathways and indicate that relative to AD non-APOE ε4 carriers, platelets and lymphocytes from AD APOE ε4 carriers exist in a relative state of bioenergetic stress. As APOE ε4 influences AD risk these data may help define a systemic AD biomarker phenotype.