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

• Published in: Neurobiology of aging Vol. 21; no. 3; pp. 455 - 462
• Main Authors: Maurer, Iris, Zierz, Stephan, Möller, Hans–Jürgen
• Format: Journal Article
• Language: English
• Published: London Elsevier Inc 01.05.2000; Elsevier Science
• Subjects: Aged; Aged, 80 and over; Alzheimer Disease - enzymology; Alzheimer disease brain; Biological and medical sciences; Brain - enzymology; Cerebral Cortex - enzymology; Cytochrome c oxidase; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Electron Transport Complex IV - metabolism; Female; Hippocampus - enzymology; Humans; Male; Medical sciences; Middle Aged; Mitochondria - enzymology; Mitochondrial respiratory chain; Neurology; Oxidative Phosphorylation; Succinate Dehydrogenase - metabolism; Cytochrome c oxidase; Alzheimer disease brain; Oxidative phosphorylation; Mitochondrial respiratory chain; Human; Nervous system diseases; Enzyme; Alzheimer disease; Central nervous system; Cytochrome-c oxidase; Cerebral disorder; Respiratory chain; Mitochondria; Central nervous system disease; Degenerative disease; Oxidoreductases; Brain (vertebrata)
• ISSN: 0197-4580; 1558-1497
• DOI: 10.1016/S0197-4580(00)00112-3

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.