title: A selective defect of cytochrome c oxidase is present in brain of Alzheimer disease patients.
abstract: To assess mitochondrial function and test the hypothesis of an underlying oxidative phosphorylation defect in Alzheimer disease (AD), we evaluated the activities of mitochondrial respiratory chain enzyme complexes I+III, complexes II+III, complex IV (cytochrome c oxidase, COX), succinate dehydrogenase, and citrate synthase in the frontal cortex, temporal cortex, hippocampus, 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 and hippocampus, both whether activities were expressed per noncollagen protein 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/mg NCP, p = 0.003) or corrected for citrate 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 dehydrogenase in any of the brain regions examined. Our results suggest a specific defect of COX in the AD brain versus the normal human brain, which may contribute to impaired energy generation. Biochemically, the defect is confined to selected brain regions, suggesting anatomic specificity.
authors.affiliation: Department of Psychiatry, Friedrich-Schiller Universität, Philosophenweg 3, 07740, Jena, Germany. maurer@landgraf.med.uni-jena.de
authors.forename: I
authors.initials: I
authors.lastname: Maurer
authors.forename: S
authors.initials: S
authors.lastname: Zierz
authors.forename: H J
authors.initials: HJ
authors.lastname: Möller
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000201:enzymology*; D001921:Brain / Q000201:enzymology*; D002540:Cerebral Cortex / Q000201:enzymology; D003576:Electron Transport Complex IV / Q000378:metabolism*; D005260:Female; D006624:Hippocampus / Q000201:enzymology; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000201:enzymology; D010085:Oxidative Phosphorylation; D013385:Succinate Dehydrogenase / Q000378:metabolism
chemical_list: D013385:Succinate Dehydrogenase; D003576:Electron Transport Complex IV