Platelet cytochrome oxidase and citrate synthase activities in APOE ε4 carrier and non-carrier Alzheimer's disease patients

A degradation product of APOE epsilon 4-encoded apolipoprotein E protein targets mitochondria and inhibits cytochrome oxidase (COX), and autopsy brains from young adult APOE epsilon 4 carriers show reduced COX activity. To further explore relationships between APOE alleles and COX, we measured platelet mitochondria COX activity in AD subjects with (n = 8) and without (n = 7) an APOE epsilon 4 allele and found the mean COX activity, when normalized to sample total protein, was lower in the APOE epsilon 4 carriers (p < 0.05). Normalizing COX activity to citrate synthase (CS) activity eliminated this difference, but notably the mean CS activity was itself lower in the APOE epsilon 4 carriers (p < 0.05). COX and CS protein levels did not appear to cause the lower APOE epsilon 4 carrier COX and CS Vmax activities. If confirmed in larger studies, these data could suggest mitochondria at least partly mediate the well-recognized association between APOE alleles and AD risk.