A selective defect of cytochrome c oxidase is present in brain of Alzheimer disease patients

To assess mitochondrial function and test the hypothesis of an underlying o xidative phosphorylation defect in Alzheimer disease (AD), we evaluated the activities of mitochondrial respiratory chain enzyme complexes I+III, comp lexes II+III, complex IV (cytochrome c oxidase, COX), succinate dt hydrogen ase, and citrate synthase in the frontal cortex, temporal cortex, hippocamp us. and cerebellum of 23 AD patients and 13 normal human brains. The major finding was a significant decrease in COX activity in AD temporal cortex an d hippocampus, both whether activities were expressed per noncollagen prote in content (49 +/- 4.6 versus 78 +/- 10.8 nmol/min/mg NCP, P = 0.006; 23 +/ - 1.9 versus 48.6 +/- 8.1 nmol/min/tng NCP, p = 0.003) or corrected for cit rate synthase activity (1.6 +/- 0.2 versus 3 +/- 0.4, P = 0.001;0.76 +/- 0. 1 versus 1.76 +/- 0.26, P = 0.0009). There were no significant differences in the activities of complexes I+III, II+III, and of succinate dehydrogenas e in any of the brain regions examined. Out results suggest a specific defe ct of COX in the AD brain versus the normal human brain, which may contribu te to impaired energy generation. Biochemically, the defect is confined to selected brain regions, suggesting anatomic specificity. (C) 2000 Elsevier Science Inc. All rights reserved.