Electron transport chain defects in Alzheimer's disease brain

Previous work suggested a deficiency in the terminal complex of the mitochondrial electron transport chain, cytochrome c oxidase (COX), in platelet mitochondria of Alzheimer's disease (AD) patients. The present study extends this observation to AD brain mitochondria through assay of electron transport chain activities in mitochondria isolated from autopsied brain samples from AD patients (n = 9) and from controls with and without known neurologic disease (n = 8). AD brain mitochondria demonstrated a generalized depression of activity of all electron transport chain complexes. This depression was most marked in COX activity (p < 0.001). Concentrations of cytochromes b, c1 and aa3 were similar in AD and controls. The electron transport chain is defective in AD brain, and the defect centers about COX.

[1]  S. Rapoport,et al.  Localization of cytochrome oxidase (COX) activity and COX mRNA in the hippocampus and entorhinal cortex of the monkey brain: correlation with specific neuronal pathways , 1992, Brain Research.

[2]  M. Beal,et al.  Does impairment of energy metabolism result in excitotoxic neuronal death in neurodegenerative illnesses? , 1992, Annals of neurology.

[3]  T. Oltersdorf,et al.  Secreted form of amyloid β protein precursor is involved in the growth regulation of fibroblasts , 1989, Cell.

[4]  K. Beyreuther,et al.  The promoter of Alzheimer's disease amyloid A4 precursor gene. , 1988, Progress in clinical and biological research.

[5]  C Hulette,et al.  The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) , 1995, Neurology.

[6]  D. Turnbull,et al.  Respiratory chain abnormalities in skeletal muscle from patients with Parkinson's disease , 1991, Journal of the Neurological Sciences.

[7]  L. Ang,et al.  Autopsy Samples of Alzheimer's Cortex Show Increased Peroxidation In Vitro , 1990, Journal of neurochemistry.

[8]  S. Ohta,et al.  Postmortem changes in mitochondrial respiratory enzymes in brain and a preliminary observation in Parkinson's disease , 1990, Journal of the Neurological Sciences.

[9]  C. Filley,et al.  Cytochrome oxidase deficiency in Alzheimer's disease , 1990, Neurology.

[10]  D. Wallace.  Mitochondrial genetics: a paradigm for aging and degenerative diseases? , 1992, Science.

[11]  R. C. Collins,et al.  Metabolic anatomy of brain: A comparison of regional capillary density, glucose metabolism, and enzyme activities , 1989, The Journal of comparative neurology.

[12]  J. Cedarbaum,et al.  Energy metabolism in disorders of the nervous system. , 1988, Revue neurologique.

[13]  J. Nobrega,et al.  Brain Cytochrome Oxidase in Alzheimer's Disease , 1992, Journal of neurochemistry.

[14]  D. Diamond,et al.  Cytochrome Oxidase Inhibition: A Novel Animal Model of Alzheimer's Disease , 1992, Journal of geriatric psychiatry and neurology.

[15]  K. Davies,et al.  The oxidative inactivation of mitochondrial electron transport chain components and ATPase. , 1990, The Journal of biological chemistry.

[16]  N. Howell,et al.  Leber hereditary optic neuropathy: involvement of the mitochondrial ND1 gene and evidence for an intragenic suppressor mutation. , 1991, American journal of human genetics.

[17]  J. Parks,et al.  Evidence for a defect in NADH , 1990, Neurology.

[18]  R. Villa,et al.  Brain cytochrome oxidase activity of synaptic and nonsynaptic mitochondria during aging. , 1989, Basic and applied histochemistry.

[19]  E. Racker,et al.  Partial resolution of the enzymes catalyzing oxidative phosphorylation. 18. The masking of adenosine triphosphatase in submitochondrial particles and its reactivation by phospholipids. , 1968, The Journal of biological chemistry.

[20]  A. Torroni,et al.  Mitochondrial oxidative phosphorylation defects in Parkinson's disease , 1992, Annals of neurology.

[21]  C. Clark,et al.  The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) , 1994, Neurology.

[22]  D. Selkoe.  Amyloid beta protein precursor and the pathogenesis of Alzheimer's disease. , 1989, Cell.

[23]  A. H. V. Schapira,et al.  MITOCHONDRIAL COMPLEX I DEFICIENCY IN PARKINSON'S DISEASE , 1989, The Lancet.

[24]  C. Filley.  Diagnosis of Alzheimer's disease. , 1988, Colorado medicine.

[25]  J. Kelly,et al.  Neuroleptic medications inhibit complex I of the electron transport chain , 1993, Annals of neurology.

[26]  F. Gabreëls,et al.  Progressive poliodystrophy (alpers') disease) with a defect in cytochromeaa3 in muscle: a report of two unrelated patients , 1983, Clinical Neurology and Neurosurgery.

[27]  W. S. Thayer,et al.  Effects of chronic ethanol intoxication on oxidative phosphorylation in rat liver submitochondrial particles. , 1979, The Journal of biological chemistry.

[28]  J. Parks,et al.  Abnormalities of the electron transport chain in idiopathic parkinson's disease , 1989, Annals of neurology.

[29]  B. Trumpower,et al.  Purification of a reconstitutively active iron-sulfur protein (oxidation factor) from succinate . cytochrome c reductase complex of bovine heart mitochondria. , 1979, The Journal of biological chemistry.

[30]  P. Greengard,et al.  Altered processing of Alzheimer amyloid precursor protein in response to neuronal degeneration. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[31]  A. Torroni,et al.  Mitochondrial oxidative phosphorylation defects in parkinson's disease , 1991, Annals of neurology.

[32]  M. Kortelainen,et al.  Long-term alcohol consumption and brown adipose tissue in man , 2004, European Journal of Applied Physiology and Occupational Physiology.

[33]  J. Lai,et al.  Preparation of synaptic and nonsynaptic mitochondria from mammalian brain. , 1979, Methods in enzymology.

[34]  W. S. Thayer.  Effects of Ethanol on Proteins of Mitochondrial Membranes a , 1987, Annals of the New York Academy of Sciences.

[35]  P. Mecocci,et al.  Oxidative damage to mitochondrial DNA shows marked age‐dependent increases in human brain , 1993, Annals of neurology.

[36]  F. Sanger,et al.  Sequence and organization of the human mitochondrial genome , 1981, Nature.

[37]  D. Curti,et al.  Oxidative Metabolism of Nonsynaptic Mitochondria Isolated from Rat Brain Hippocampus: A Comparative Regional Study , 1988, Journal of neurochemistry.

[38]  S. Rapoport,et al.  Differential expression of cytochrome oxidase (COX) genes in different regions of monkey brain , 1992, Journal of neuroscience research.

[39]  J. Blass,et al.  The role of oxidative abnormalities in the pathophysiology of Alzheimer's disease. , 1991, Revue neurologique.

[40]  M. Wong-Riley,et al.  Brain cytochrome oxidase: purification, antibody production, and immunohistochemical/histochemical correlations in the CNS , 1989, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[41]  O. H. Lowry,et al.  Protein measurement with the Folin phenol reagent. , 1951, The Journal of biological chemistry.

[42]  M. Haak,et al.  Hamster cell mutants unable to grow on galactose and exhibiting an overlapping complementation pattern are defective in the electron transport chain. , 1981, The Journal of biological chemistry.

[43]  Y. Hatefi,et al.  Resolution of complex I and isolation of NADH dehydrogenase and an iron--sulfur protein. , 1978, Methods in Enzymology.

[44]  S H Appel,et al.  A unifying hypothesis for the cause of amyotrophic lateral sclerosis, parkinsonism, and alzheimer disease , 1981, Annals of neurology.