Abstract
There is a compelling need to understand neuronal oxidative metabolism in Alzheimer’s brains in order to unequivocally diagnose and treat Alzheimer’s disease patients successfully. This disease may be affecting one of every three families in the US. Although rare familial types of Alzheimer’s disease follow Mendelian genetics, most cases appear after age 65 and have no clearly identifiable nuclear genetic defects. It is in this majority of late-onset, sporadic cases that defects in cytochrome oxidase activity have been linked to mitochondrial DNA mutations. Recent mounting evidence suggests that a cytochrome oxidase catalytic defect with mitochondrial DNA oxidative damage is a reliable marker of sporadic Alzheimer’s disease. With advancing age, chronic inhibition of cytochrome oxidase activity produces neuronal metabolic failure and memory dysfunction. Cytochrome oxidase inhibition leads to senile dementia and neurodegeneration in late-onset Alzheimer’s disease in a cascade of multiple intracellular events, initiated primarily by neuronal aerobic energy depletion, mitochondrial formation of reactive oxygen species and disruption of intracellular calcium homeostasis. Quantitative cytochemical methods for assessing cytochrome oxidase activity in individual cells are described in detail. Cytochemical findings are discussed in relationship to the selective vulnerability of metabolically active larger projection neurons in Alzheimer’s brains. Additional results are presented that suggest that muscle biopsy may be used as an early diagnostic aid in living subjects suspected of sporadic Alzheimer’s disease. The data support the hypothesis that sporadic Alzheimer’s disease is a systemic mitochondrial disease, characterized by cytochrome oxidase inhibition. Early in sporadic Alzheimer’s disease the inhibition of neuronal cytochrome oxidase activity is caused by a systemic cytochrome oxidase defect. The brain is proposed to be the most vulnerable organ to show primary oxidative pathogenesis as a result of systemic cytochrome oxidase inhibition. Possible treatments for neuronal oxidative stress in Alzheimer’s disease are proposed.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Aggleton, J.P. (Ed.), 1992, The Amygdala: Neurobiological Aspects of Emotion, Memory, and Mental Dysfunction. New York: Wiley-Liss.
Akaaboune, M., Villanova, M., Festoff, B.W., Verdiere-Sahuque, M., & Hantai, D., 1994, Apolipoprotein E expression at neuromuscular junctions in mouse, rat and human skeletal muscle, FEBS Letters, 351, 246–248.
Arai, H., 1996, Biological markers for the clinical diagnosis of Alzheimer’s disease. Tohoku Journal ofExperimental Medicine, 179, 65–79.
Arendt, T., Bigl, V., Arendt, A., & Tennstedt, A., 1983, Loss of neurons in the nucleus basalis of Meynert in Alzheimer’s disease, paralysis agitans and Korsakoff’s disease. Acta Neuropathologica, 61, 101–108.
Ball, M.J., Fisman, M., Hachinski, V., Blume, W., Fox, A., Kral, V.A., Kirshen, A.J., Fox, H., & Merskey, H.,1985, A new definition of Alzheimer’s disease: A hippocampal dementia. Lancet, 1, 14–16.
Bauserman, S.C. & Heffner, R.R., 1984, Mitochondrial myopathies. In Heffner, R.R. (Ed.), Muscle Pathology, L.W. Roth, Series Ed., Churchill-Livingstone, Inc., New York.
Beal, M.F., 1992a, Does impairment of energy metabolism result in excitotoxic neuronal death in neurodegenerative illnesses? Annals of Neurology, 31, 119–130.
Beal, M.F., 1992b, Mechanisms of excitotoxicity in neurologic diseases. The FASEB Journal, 6, 3338–3342.
Beal, M.F.; Howell, N.; Bodis-Wollner, I. (Eds.), 1997, Mitochondria and Free Radicals in Neurodegenerative Diseases. New York: Wiley-Liss.
Beal, M.F., Hyman, B.T., & Koroshetz, W., 1993, Do defects in mitochondrial energy metabolism underlie the pathology of neurodegenerative disorders? Trends in Neurosciences, 16, 125–131.
Becker. W., Reece, J.B., & Peonie, M.F., 1996, The World of the Cell. Menlo Park: Benjamin/Cummings Publishing Company.
Behl, C., Davis, J., Cole, G.M., & Schubert, D., 1992, Vitamin E protects nerve cells from amyloid beta protein toxicity. Biochemical and Biophysical Research Communications, 186, 944–950.
Behl, C., Widmann, M., Trapp, T., & Holsboer, F., 1995, 17-beta estradiol protects neurons from oxidative stressinduced cell death in vitro. Biochemical and Biophysical Research Communications, 216, 473–482.
Behl, C., Trapp, T., Skutella. T., & Holsboer, F., 1997, Protection against oxidative stress-induced neuronal cell death-a novel role for RU486. European Journal of Neuroscience, 9,9I2–920.
Betel, C., Skutella, T., Lezoualc’h, F., Post, A., Widmann, M., Newton, C.J., & Holsboer, F., 1997, Neuroprotection against oxidative stress by estrogens: structure-activity relationship. Molecular Pharmacology, 51, 535–541.
Bennett, M.C., & Rose, G.M., 1992, Chronic sodium azide treatment impairs learning of the Morris water maze task. Behavioral and Neural Biology, 58, 72–75.
Bennett, M.C., Diamond, D.M., Parker, W.D., Jr., Stryker, S.L., & Rose, G.M., 1992a, Inhibition of cytochrome oxidase impairs learning and hippocampal plasticity: a novel animal model of Alzheimer’s disease. In J. Simpkins, F.T. Crews, & E.M. Meyer (Eds.), Alzheimer’s Disease Therapy: A New Generation of Progress, pp. 485–501, New York: Plenum Press.
Bennett, M.C., Diamond, D.M., Stryker, S.L., Parks, J.K., & Parker, W.D., Jr., 1992b, Cytochrome oxidase inhibition: a novel animal model of Alzheimer’s disease. Journal of Geriatric Psychiatry and Neurology, 5, 93–101.
Biegon, A., & Wolff, M., 1986, Quantitative histochemistry of acetylcholinesterase in rat and human brain postmortem. Journal of Neuroscience Methods, 16, 39–45.
Blass, J.P., Sheu, R.K.F., & Cedarbaum, J.M., 1988, Energy metabolism in disorders of the nervous system. Revue Neurologique, 144, 543–563.
Blass, J.P., 1993, Metabolic alterations common to neural and non-neural cells in Alzheimer’s disease. Hippocampus, 3 Spec No, 45–53.
Bloch, V., 1976, Brain activation and memory consolidation. In M.R. Rosenzweig & E.L. Bennett (Eds.), Neural Mechanisms of Learning and Memory, pp. 582–590, Cambridge, Massachusetts: MIT Press.
Boveris, A., & Chance, B., 1973, The mitochondrial generation of hydrogen peroxide: General properties and the effect of hyperbaric oxygen. Biochemical Journal, 134, 707–716.
Cada, A.. Gonzalez-Lima, F., Rose, G.M., & Bennett, M.C., 1995, Regional brain effects of sodium azide treatment on cytochrome oxidase activity: A quantitative histochemical study. Metabolic Brain Disease, 10, 303–319.
Carney, J.M., & Floyd, R.A., 1991, Protection against oxidative damage to CNS by alpha-phenyl-tert-butyl nitrone, PBN) and other spin-trapping agents: a novel series of nonlipid free radical scavengers. Journal of Molecular Neuroscience, 3, 47–57.
Chagnon, P., Betard, C., Robitaille, Y., Cholette, A.. Gauvreau, & D., 1995, Distribution of brain cytochrome oxidase activity in various neurodegenerative diseases. Neuroreport, 6, 711–715.
Chandrasekaran, K., Stoll, J.. Giordano, T., Atack, J.R., Matocha, M.F., Brady, D.R., & Rapoport, S.I., 1992, Differential expression of cytochrome oxidase, COX) genes in different regions of monkey brain. Journal of Neuroscience Research, 32, 41 5–423.
Chandrasekaran, K., Giordano, T., Brady, D.R., Stoll, J., Martin, L.J., & Rapoport, S.I., 1994, Impairment in mitochondrial cytochrome oxidase gene expression in Alzheimer’s disease. Molecular Brain Research, 24, 336–340.
Coomber, P., Crews, D., & Gonzalez-Lima, F., 1997, Independent effects of incubation temperature and gonadal sex on the volume and metabolic capacity of brain nuclei in the leopard gecko, Eublepharismacularius), a lizard with temperature-dependent sex determination. Journal of Comparative Neurology, 380, 409–421.
Curti, D., Giangare, M.C., Redolfi, M.E., Fugaccia, I., & Benzi, G., 1990, Age-related modifications of cytochrome r oxidase activity in discrete brain regions. Mechanisms of Ageing and Development, 55, 171–180.
Davis, R.E., Miller, S., Herrnstadt, C., Ghosh, S.S., Fahy, E., Shinobu, L.A., Galasko, D., Thal, L.J., Beal, M.F., Howell, N., and Parker, W.D., 1997, Mutations in mitochondrial cytochrome c oxidase genes segregate with late-onset Alzheimer disease. Proceedings of the National Academy of Sciences, 94, 4526–4531.
de la Torre, J.C., Cada, A., Nelson, N., Davis, G., Sutherland, R.J., & Gonzalez-Lima, F., 1997, Reduced cytochrome oxidase and memory dysfunction after chronic brain ischemia in aged rats. Neuroscience Letters, 223, 165–168.
de Leon, M.J., Convit, A., George, A.E., Golomb, J., de Santi, S., Tarshish, C., Rusinek, H., Bobinski, M., Ince, C., Miller, D., & Wisniewski, H., 1996, In vivo structural studies of the hippocampus in normal aging and in incipient Alzheimer’s disease. Annals of the New York Academy of Sciences,777,1–13.
Dykens, J.A., 1997, Mitochondrial free radical production and oxidative pathophysiology: implications for neurodegenerative diseases. In M.F. Beal, N. Howell, & I. Bodis-Wollner (Eds.), Mitochondria and Free Radicals in Neurodegenerative Diseases, pp. 29–56, New York: Wiley-Liss.
Gabbita, S.P., Butterfield D.A., & Carney, J.M., 1997, Neurodegeneration and potential antioxidant-based therapeutic approaches. In M.F. Beal, N. Howell, & I. Bodis-Wollner (Eds.), Mitochondria and Free Radicals in Neurodegenerative Diseases, pp. 497–512, New York: Wiley-Liss.
Gonzalez-Lima, E.M., & Gonzalez-Lima, F., 1987, Sources of stress affecting caregivers of Alzheimer’s disease patients. Health Values, 1l, 3–10.
Gonzalez-Lima, F., & Scheich, H., 1985, Ascending reticular activating system in the rat: A 2- deoxyglucose study. Brain Research, 344, 70–88.
Gonzalez-Lima, F., & Garrosa, M., 1991, Quantitative histochemistry of cytochrome oxidase in rat brain. Neuroscience Letters, 123, 251–253.
Gonzalez-Lima, F., 1992, Brain imaging of auditory learning functions in rats: Studies with fluorodeoxyglucose autoradiography and cytochrome oxidase histochemistry. In F. Gonzalez-Lima, T. Finkenstadt, & H. Scheich (Eds.), Advances in Metabolic Mapping Techniques for Brain Imaging of Behavioral and Learning Functions, NATO ASI Vol. D68, pp. 39–109, The Netherlands: Kluwer Academic Publishers.
Gonzalez-Lima, F., Helmstetter, F.J., & Agudo,.1., 1993, Functional mapping of the rat brain during drinking behavior: A fluorodeoxyglucose study. Physiology and Behavior, 54, 605–612.
Gonzalez-Lima, F., & Jones, D., 1994, Quantitative mapping of cytochrome oxidase activity in the central auditory system of the gerbil: A study with calibrated activity standards and metal-intensified histochemistry. Brain Research, 660, 34–49.
Gonzalez-Lima, F., & Cada, A., 1994, Cytochrome oxidase activity in the auditory system of the mouse: A qualitative and quantitative histochemical study. Neuroscience, 63, 559–578.
Gonzalez-Lima, F., & McIntosh, A.R., 1996, Conceptual and methodological issues in the interpretation of brain-behavior relationships. In R.W. Thatcher, G.R. Lyon, J. Ramsey, & N. Krasnegor (Eds.), Developmental Neuroimaging: Mapping the Development of Brain and Behavior; pp. 235–253, Orlando, Florida: Academic Press.
Gonzalez-Lima, F., Valla, J., and Matos-Collazo, S., 1997, Quantitative cytochemistry of cytochrome oxidase and cellular morphometry of the human inferior colliculus in control and Alzheimer’s patients. Brain Research, 752, 117–126.
Gonzalez-Lima, F., Valla, J., & Cada, A., 1998, Brain cytochrome oxidase activity and how it relates to the pathophysiology of memory and Alzheimer’s disease. In T. Ozben (Ed.), Free Radicals, Oxidative Stress and Antioxidants: Pathological and Physiological Significance. New York: Plenum Press.
Grimes, A.M., Grady, C.L., Foster, N.L., Sunderland, T.. & Patronas, N.J., 1985. Central auditory function in Alzheimer’s disease. Neurology, 35, 352–358.
Gunther, T.E., & Pfeiffer, D.R., 1990, Mechanisms by which mitochondria transport calcium. ArnericanJournal of Physiology, 258, c755 - c786
Harman, D., 1988, Free radicals in aging. Molecular and Cellular Biochemistry, 84, 155–161.
Henderson, V.W., 1997, The epidemiology of estrogen replacement therapy and Alzheimer’s disease. Neurology’, 48, S27 - S35
Hensley, K., Carney, J.M., Stewart, C.A., Tabatabaie, T., Pye, Q., & Floyd, R.A., 1997, Nitrone-based free radical traps as neuroprotective agents in cerebral ischaemia and other pathologies. international Review of Neurobiology, 40, 299–317.
Hess, H.H., & Pope, A., 1953, Ultramicrospectrophotometric determination of cytochrome oxidase for quantitative histochemistry. Journal of Biological Chemistry, 209, 295–306.
Hevner, R.F., & Wong-Riley, M.T.T., 1989, Brain cytochrome oxidase: purification, antibody production, and immunohistochemical/histochemical correlations in the CNS. Jounal of Neuroscience, 9, 3884–3898.
Hevner, R.F., Duff, R.S., & Wong-Riley, M.T.T., 1992, Coordination of ATP production and consumption in brain: parallel regulation of cytochrome oxidase and NA+, K+-ATPase. Neuroscience Letters, 138, 188–192.
Hevner, R.F., Liu, S., & Wong-Riley, M.T.T., 1993, An optimized method for determining cytochrome oxidase activity in brain tissue homogenates. Journal of Neuroscience Methods, 50, 309–319.
Huidobro, A., Blanco, P., Villalba, M., Gomez-Puertas, P., Villa, A., Pereira, R., Bogonez, E., Martinez-Serrano, A., Aparicio, J.J., & Satrustegui, J., 1993, Age-related changes in calcium homeostatic mechanisms in synaptosomes in relation with working memory deficiency. Neurobiology of Aging. 14, 479–486.
Ihara, Y., 1988, Massive somatodendritic sprouting of cortical neurons in Alzheimer’s disease. Brain Research, 459, 138–144.
Iwamoto, N., Thangnipon, W., Crawford, C., & Emson, P.C., 1991, Localization of calpain immunoreactivity in senile plaques and in neurones undergoing neurofibrillary degeneration in Alzheimer’s disease. Brain Research, 561, 177–180.
Kawas, C., Resnick, S., Morrison, A., Brookmeyer, R.. Corrada, M.. Zonderman, A., Bacal, C., Lingle, D.D., & Metter, E., 1997, A prospective study of estrogen replacement therapy and the risk of developing Alzheimer’s disease: the Baltimore Longitudinal Study of Aging. Neurology, 48, 1517–1521.
Kish, S.J., Bergeron, C’., Rajput, A., Dozic, S., Mastrogiacomo, F., Chang, L., Wilson, J.M., DiStefano, L.M., & Nobrega, J.N., 1992, Brain cytochrome oxidase in Alzheimer’s disease. Journal of Neurochemistr v, 59, 776–779.
Kish, S.J., 1997, Brain energy metabolizing enzymes in Alzheimer’s disease: alpha-ketoglutarate dehydrogenase complex and cytochrome oxidase. In J.C. de la Torre and V. Hachinski (Eds.), Cerebrovaxciilar Pathology in A1=heinters Disease, pp. 218 228, New York: New York Academy of Sciences.
Landin, K., Blennow, K., Wallin, A., & Gottfries, C.G., 1993, Low blood pressure and blood glucose levels in Alzheimer’s disease: Evidence for a hypometabolic disorder ? Journal of Internal Medicine, 233, 257–363.
Lowry, O.H., Rosebrough, N.J., Farr, A.L., & Randall, R.J., 1951. Protein measurement with the folin phenol reagent. Journal of Biological Chemistry, 193, 295–275.
Maurizi, C.P., 1997, Loss of intraventricular fluid melatonin can explain the neuropathology of Alzheimer’s disease. Medical Hypotheses., 49, 153–158.
McEwen, B.S., Alves, S.E., Bulloch, K., & Weiland, N.G., 1997, Ovarian steroids and the brain: implications for cognition and aging. Neurology, 48, S8 - S15
Mecocci, P., MacGarvey, U., & Beal, M.F., 1994, Oxidative damage to mitochondria) DNA is increased in Alzheimer’s disease. Annals ofNeurology, 36, 747–751.
Meier-Ruge, W., Bertoni-Freddari, C., & Iwangoff, P., 1994, Changes in brain glucose metabolism as a key to the pathogenesis of Alzheimer’s disease. Gerontology, 40, 246–252.
Meier-Ruge, W.A., and Bertoni-Freddari, C., 1997, Pathogenesis of decreased glucose turnover and oxidative phosphorylation in ischemic and trauma-induced dementia of the Alzheimer type. In J.C. de la Torre and V. Hachinski (Eds.), Cerebrovaseular Pathology in Alzheimer’s Disease, pp. 229–241, New York: New York Academy of Sciences.
Mutisya, E.M., Bowling, A.C., & Beal, M.F., 1994, Cortical cytochrome oxidase activity is reduced in Alzheimer’s disease. Journal of Neurochemistry, 63, 2179–2184.
Nicotera, P., Bellomo, G., & Orrenius. S., 1990, The role ofCa2+ in cell killing. Chemical Research in Toxicology, 3, 484–494.
Nixon, R.A., & Cataldo, A.M.. 1994, Free radicals, proteolysis, and the degeneration of neurons in Alzheimer disease: How essential is the b-amyloid link? Neurobiology of Aging, 15, 463–469.
Nobrega, J.N., 1992, Brain metabolic mapping and behavior: Assessing the effects of early developmental experiences in adult animals. In F. Gonzalez-Lima, T. Finkenstaedt, & H. Scheich (Eds.), Advances in Metabolic Mapping Techniques for Brain Imaging of Behavioral and Learning Functions, NATO ASI Vol. D68, pp. 125–149, Dordrecht/Boston/London: Kluwer Academic Publishers.
Nobrega, J.N., Raymond. R., DiStefano, L., & Burnham, W.M., 1993, Long-term changes in regional brain cytochrome oxidase activity induced by electroconvulsive treatment in rats. Brain Research, 605, 1–8.
Ohm, T.G., & Braak, H., 1989, Auditory brainstem nuclei in Alzheimer’s disease. Neuroscience Letters, 96. 60–63.
Olton, D.S., Wible, C.G., Pang, K.. & Sakurai, Y., 1989, Hippocampal calls have mnemonic correlates as well as spatial ones. Psychobiology, 17, 228–229.
Paganini-Hill, A., & Henderson, V.W., 1996, Estrogen replacement therapy and risk of Alzheimer disease. Archives of Internal Medicine. 156, 2213–2217.
Parker, W.D., Jr., Filley, C.M., & Parks, J.K., 1990, Cytochrome oxidase deficiency in Alzheimer’s disease. Neurology, 40, 1302–1303.
Parker, W.D., Jr., 1991, Cytochrome oxidase deficiency in Alzheimer’s disease. Annals of the New York Academy of Sciences, 640, 59–64.
Parker, W.D., Jr., Mahr, N.J., Filley, C.M., Parks, J.K., Hughes, M.A., Young, D.A., & Cullum, C.M., I994a, Reduced platelet cytochrome c oxidase activity in Alzheimer’s disease. Neurology, 44, 1086–1090.
Parker, W.D., Jr., Parks, J., Filley, C.M., & Kleinschmidt-DeMasters, B.K., 1994b, Electron transport chain defects in Alzheimer’s disease brain. Neuoologi’, 44, 1090–1096.
Parker. W.D., Jr., & Davis, R.E., 1997, Primary mitochondrial DNA defects as a causative event in Alzheimer’s disease. In M.F. Beal, N. Howell, & I. Bodis-Wollner (Eds.), Mitochondria and Free Radicals in Neurodegenerative Diseases, pp. 319–334, New York: Wiley-Liss.
Partridge, R.S., Monroe, S.M., Parks, J.K., Johnson, K., Parker, W.D., Jr., Eaton, G.R., & Eaton, S.S., 1994, Spin trapping of azidyl and hydroxyl radicals in azide-inhibited submitochondrial particles. Archives of Biochemistry and Biophysics, 310, 210–217.
Pettegrew, J.W., Klunk, W.E., Panchalingam, K., Kanfer, J.N., & McClure, R.J., 1995, Clinical and neurochemical effects of acetyl-L-carnitine in Alzheimer’s disease. Neurobiology of Aging, 16, 1–4.
Pettegrew, J.W., Klunk, W.E., Panchalingam, K., McClure. R.J., and Stanley, J.A., 1997, Magnetic resonance spectroscopic changes in Alzheimer’s disease. In J.C. de la Torre & V. Hachinski (Eds.), Cerebrovascular Patlologi: in AL - heimer’s Disease, pp. 282–306, New York: New York Academy of Sciences.
Radi, R., Castro, L., Rodriguez, M., Cassina, A., & Thomson, L., 1997, Free radical damage to mitochondria. In M.F. Beal, N. Howell, and I. Bodis-Wollner (Eds.), Mitochondria and Free Radicals in Neurodegenerative Diseases,pp. 57–90, New York: Wiley-Liss.
Reiman, E.M., Caselli, R.J., Yun, L.S., Chen, K., Bandy, D., Minoshima, S.. Thibodeau, S.N., & Osborne, D., 1996, Preclinical evidence of Alzheimer’s disease in persons homozygous for the epsilon 4 allele for apolipoprotein E. New England Journal of Medicine, 334, 752–758.
Richter, C., & Kass, G.E.N., 1991, Oxidative stress in mitochondria: its relationship to cellular Ca2+ homeostasis, cell death, proliferation, and differentiation. Chemico-Biological Interactions, 77, 1–23.
Richter, C., 1995, Oxidative damage to mitochondrial DNA and its relationship with aging. International Journal of Biochemistry and Cell Biology, 27, 647–653.
Saitoh, T., Sundsmo, M., Roch, J., Kimura, N., Cole, G., Schubert, D., Oltersdorf, T., & Schenk. D.B., 1989, Secreted form of amyloid protein precursor is involved in the growth regulation of fibroblasts. Cell. 58, 615–622.
Sarnat, H.B., 1983, Muscle Pathology and Histochemistry, Chicago: American Society of Clinical Pathologists Press.
Sayre, L.M., Zelasko, D.A., Harris, P.L., Perry, G., Salomon, R.G., & Smith. M.A., 1997, 4-Hydroxynonenal-derived advanced lipid peroxidation end products are increased in Alzheimer’s disease. Journal of Neurochemistry, 68, 2092–2097.
Schlaepfer, W.W., Lee, C., Lee, V., & Zimmerman, U.J., 1985, An immunoblot study of neurofilament degradation in situ and during calcium-activated proteolysis. Journal of Neurochemistry. 44, 502–509.
Seligman, A.M., Karnovsky, M.J., Wasserkrug, H.L., & Hanker, J.S., 1968, Nondroplet ultrastructural demonstration of cytochrome oxidase activity with a polymerizing osmiophilic reagent, diaminobenzidine, DAB, Journal of Cell Biology, 38, 1–14.
Sherwin, B.B., 1997, Estrogen effects on cognition in menopausal women. Neurology, 48, 521 - S26
Shimohama, S., Suenaga, T., Araki, W., Yamaoaka, Y., Shimizu, K., & Kimura, J., 1991, Presence of calpain II immunoreactivity in senile plaques in Alzheimer’s disease. Brain Research, 558, 105–108.
Siman, R., Card, J.P., & Davis, L.G., 1990, Proteolytic processing of B-amyloid precursor by calpain 1. Journal of Neuroscience, 10, 2400–2411.
Sinha, U.K., Hollen, K.M., Rodriguez, R., & Miller, C.A., 1993, Auditory system degeneration in Alzheimer’s disease. Neurology, 43, 779–785.
Smith, M.A., Lawrence, S.M., Monnier, V.M., & Perry, G., 1995a, Radical ageing in Alzheimer’s disease. Trends in Neuroscience, 18, 172–176.
Smith, M.A., Rudnicka-Nawrot, M., Richey, P.L., Prapotnik, D., Mulvihill, P., Miller, C.A., Sayre, L.M., & Perry, G., 1995b, Carbonyl-related posttranslational modification of neurofilament protein in the neurofibrillary pathology of Alzheimer’s disease. Journal of Neurochemistry, 64, 2660–2666.
Smith, M.A., Perry, G., Richey, P.L., Sayre, L.M., Anderson, V.E., Beal, M.F., & Kowall, N., 1996a, Oxidative damage in Alzheimer’s. Nature, 382, 120–121.
Smith, M.A., Sayre, L., & Perry, G., 1996b, Is Alzheimer’s a disease of oxidative stress’? Alzheimer’s Disease Review, 1, 63–67.
Smith, M.A., Richey-Harris, P.L., Sayre, L.M., Beckman, J.S., & Perry, G., 1997, Widespread peroxynitrite-mediated damage in Alzheimer’s disease. Journal of Neuroscience, 17, 2653–2657.
Sohal, R.S., 1997, Role of mitochondria and oxidative stress in the aging process. In M.F. Beal, N. Howell, and I. Bodis-Wollner (Eds.), Mitochondria and Free Radicals in Neurodegenerative Diseases, pp. 91–108, New York: Wiley-Liss.
Sokoloff, L., 1989, Circulation and energy metabolism of the brain. In G.J. Siegel, B.W. Agranoff, R.W. Albers, & P. Molinoff (Eds.), Basic Neurochemistry, pp. 471–495, Boston: Little Brown.
Southorn, P.A., & Powis, G., 1988, Free radicals in medicine. Mayo Clinic Proceedings, 63, 381–408.
Spagnoli, A., Lucca, U., Menasce, G., Bandera, L., Cizza, G., Forloni, G., Tettamanti, M., Frattura, L., Tiraboschi, P., & Comelli, M., 1991, Long-term acetyl-L-camitine treatment in Alzheimer’s disease. Neurology, 41, 1726–1732.
Terwel, D., Prickaerts, J., Meng, F., & Jolles, J., 1995, Brain enzyme activities after intracerebroventricular injection of streptozotocin in rats receiving acetyl-L-carnitine. European Journal of Pharmacology, 287, 65–71.
Uchida, Y., Ihara, Y., & Tomonaga, M., 1988, Alzheimer’s disease brain extract stimulates the survival of cerebral cortical neurons from neonatal rats. Biochemical and Biophysical Research Communications, 150, 1263–1267.
Van Hoesen, G.W., 1990, The dissection by Alzheimer’s disease of cortical and limbic neural systems relevant to memory. In J.L. McGaugh, N.M. Weinberger, and G. Lynch (Eds.), Brain Organization and Memory: Cells, Systems, and Circuits, pp. 234–261, New York: Oxford University Press.
Van Zuylen, A.J., Bosman, G.J., Ruitenbeek, W., Van Kalmthout, P.J., & De Grip, W.J., 1992, No evidence for re- duced thrombocyte cytochrome oxidase activity in Alzheimer’s disease. Neurology 42, 1246–1247.
Wharton, D.C., & Tzagoloff, A., 1967, Cytochrome oxidase from beef heart mitochondria. Methods of Enzymology, 10, 245–250.
Wikstrom, M., Krab, K., & Saraste, M., 1981, Cytochrome oxidase: A synthesis. New York: Academic Press.
Wong-Riley, M.T.T., Merzenich, M.M., & Leake, P.A., 1978, Changes in endogenous reactivity to DAB induced by neuronal inactivity. Brain Research, 141, 185–192.
Wong-Riley, M.T.T., 1979, Changes in the visual system of monocularly sutured or enucleated cats demonstrated with cytochrome oxidase histochemistry. Brain Research, 171, 11–28.
Wong-Riley, M.T.T., & Riley, D.A., 1983, The effect of impulse blockage on cytochrome oxidase activity in the cat visual system. Brain Research, 261, 185–193.
Wong-Riley, M.T.T., 1989, Cytochrome oxidase: an endogenous metabolic marker for neuronal activity. Trends in Neurosciences, 12, 94–101.
Yan, S.D., Chen, X., Schmidt, A.M., Brett, J., Godman, G., Zou, Y.S., Scott, C.W., Caputo, C., Frappier, T., Smith, M.A., Perry, G., Yen, S.H., & Stern, D., 1994, Glycated tau protein in Alzheimer’s disease: a mechanism for induction of oxidant stress. Proceedings of the National Academy of Sciences, 91, 7787–7791.
Yan, S.D., Yan, S.F., Chen, X., Fu, J., Chen, M., Kuppusamy, P., Smith, M.A., Perry, G., Godman, G.C., Nawroth, P., Zweier, J.L., & Stern, D., 1995, Non-enzymatically glycated tau in Alzheimer’s disease induces neuronal oxidant stress resulting in cytokine gene expression and release of amyloid beta-peptide. Nature Medicine, 1, 693–699.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1998 Springer Science+Business Media New York
About this chapter
Cite this chapter
Gonzalez-Lima, F., Valla, J., Jorandby, L. (1998). Cytochrome Oxidase Inhibition In Alzheimer’s Disease. In: Gonzalez-Lima, F. (eds) Cytochrome Oxidase in Neuronal Metabolism and Alzheimer’s Disease. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-9936-1_6
Download citation
DOI: https://doi.org/10.1007/978-1-4757-9936-1_6
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4757-9938-5
Online ISBN: 978-1-4757-9936-1
eBook Packages: Springer Book Archive