Cytochrome oxidase deficiency in Alzheimer’s disease
Abstract
We assayed cytochrome oxidase and other electron transport chain activities in platelet mitochondria isolated from patients with Alzheimer's disease (AD). Five of 6 patients had striking reductions of platelet cytochrome oxidase activity (patient mean, 83.72 +/- 82.99 nmol/min/mg; control mean, 167.14 +/- 36.21 nmol/min/mg; n = 8). Other electron transport chain catalytic activities were not significantly different than control values. AD may be a systemic illness, a primary defect in cytochrome oxidase may be pathogenically important in its production, and the mitochondrial genes encoding cytochrome oxidase subunits may be important in producing the defect.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In mitochondria isolated from AD platelets, the activity of complex IV, or cytochrome c oxidase, is significantly decreased.
“however, in mitochondria isolated from AD platelets, the activity of complex IV, or cytochrome c oxidase, is significantly decreased [109,110,111]”
From Mitochondrial Oxidative and Nitrosative Stress and Alzheimer Disease (2020) · cites this paper as [109]
Reduced COX activity is also seen in AD subject platelets and fibroblasts.
“In addition to the brain, reduced COX activity is also seen in AD subject platelets and fibroblasts [127, 128].”
From Brain aging, Alzheimer's disease, and mitochondria (2011) · cites this paper as [127]
Cited by
Sorted by citations
Mitochondrial Dysfunction and Oxidative Stress in Neurodegenerative Diseases
Lin, M. T., & Beal, M. F. (2006) · Nature · doi:10.1038/nature05292 · Cited by 6,455 · see citing works
Aging, energy, and oxidative stress in neurodegenerative diseases
Beal, M. F. (1995) · Annals of Neurology · doi:10.1002/ana.410380304 · Cited by 1,434 · see citing works
Excess brain protein oxidation and enzyme dysfunction in normal aging and in Alzheimer disease.
Smith, C. D., Carney, J. M., Starke-Reed, P. E., Oliver, C. N., Stadtman, E. R., Floyd, R. A., & Markesbery, W. R. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.23.10540 · Cited by 1,296 · see citing works
Mitochondrial Genetics: A Paradigm for Aging and Degenerative Diseases?
Wallace, D. C. (1992) · Science · doi:10.1126/science.1533953 · Cited by 1,256 · see citing works
Oxidative damage to mitochondrial DNA is increased in Alzheimer’s disease
Mecocci, P., MacGarvey, U., & Beal, M. F. (1994) · Annals of Neurology · doi:10.1002/ana.410360510 · Cited by 1,037 · see citing works
Reddy, P. H., & Beal, M. F. (2008) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2007.12.002 · Cited by 975 · see citing works
Beal, M. F. (1992) · Annals of Neurology · doi:10.1002/ana.410310202 · Cited by 956 · see citing works
Oxidative stress in Alzheimer’s disease
Smith, M. A., Rottkamp, C. A., Nunomura, A., Raina, A. K., & Perry, G. (2000) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/s0925-4439(00)00040-5 · Cited by 895 · see citing works
Mitochondrial DNA deletions in human brain: regional variability and increase with advanced age
Corral-Debrinski, M., Horton, T., Lott, M. T., Shoffner, J. M., Flint Beal, M., & Wallace, D. C. (1992) · Nature Genetics · doi:10.1038/ng1292-324 · Cited by 890 · see citing works
Mitochondria and Mitochondrial Cascades in Alzheimer’s disease
Swerdlow, R. H. (2018) · Journal of Alzheimer’s Disease · doi:10.3233/jad-170585 · Cited by 850 · see citing works
“cytochrome oxidase (COX) activity [21].”
BackgroundDevi, L., Prabhu, B. M., Galati, D. F., Avadhani, N. G., & Anandatheerthavarada, H. K. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.1469-06.2006 · Cited by 792 · see citing works
“Altered mitochondrial fluidity and the activity of mitochondrial cytochrome c oxidase, which is the terminal oxidase in the respiratory chain, have been reported to be low in the AD brains (Parker, 1991; Sims, 1996; Maurer et al., 2000).”
BackgroundThe Alzheimer’s disease mitochondrial cascade hypothesis: progress and perspectives
Swerdlow, R. H., Burns, J. M., & Khan, S. M. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.09.010 · Cited by 786 · see citing works
The NADH:ubiquinone oxidoreductase (complex I) of respiratory chains
Walker, J. E. (1992) · Quarterly Reviews of Biophysics · doi:10.1017/s003358350000425x · Cited by 777 · see citing works
A “mitochondrial cascade hypothesis” for sporadic Alzheimer’s disease
Swerdlow, R. H., & Khan, S. M. (2004) · Medical Hypotheses · doi:10.1016/j.mehy.2003.12.045 · Cited by 758 · see citing works
Bains, J. S., & Shaw, C. A. (1997) · Brain Research Reviews · doi:10.1016/s0165-0173(97)00045-3 · Cited by 716 · see citing works
Rajmohan, R., & Reddy, P. H. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-160612 · Cited by 695 · see citing works
Hansson Petersen, C. A., Alikhani, N., Behbahani, H., Wiehager, B., Pavlov, P. F., Alafuzoff, I., Leinonen, V., Ito, A., Winblad, B., Glaser, E., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0806192105 · Cited by 693 · see citing works
Consensus Report of the Working Group on: “Molecular and Biochemical Markers of Alzheimer’s Disease”
The Ronald and Nancy Reagan Research Institute of the Alzheimer’s Association and, & National Institute on Aging Working Group (1998) · Neurobiology of Aging · doi:10.1016/s0197-4580(98)00022-0 · Cited by 702 · see citing works
Origin and functional consequences of the complex I defect in Parkinson's disease
Swerdlow, R. H., Parks, J. K., Miller, S. W., Davis, R. E., Tuttle, J. B., Trimmer, P. A., Sheehan, J. P., Bennett, J. P., & Parker, W. D. (1996) · Annals of Neurology · doi:10.1002/ana.410400417 · Cited by 638 · see citing works
Self-citationSchapira, A. H. V. (2006) · The Lancet · doi:10.1016/s0140-6736(06)68970-8 · Cited by 594 · see citing works
Do defecs in mitochondrial energy metabolism underlie the pathology of neurodegenerative diseases?
Beal, M. F., Hyman, B. T., & Koroshetz, W. J. (1993) · Trends in Neurosciences · doi:10.1016/0166-2236(93)90117-5 · Cited by 574 · see citing works
Anandatheerthavarada, H. K., Biswas, G., Robin, M.-A., & Avadhani, N. G. (2003) · The Journal of Cell Biology · doi:10.1083/jcb.200207030 · Cited by 571 · see citing works
“…$8.00 The Journal of Cell Biology, Volume 161, Number 1, April 14, 2003 41–54 http://www.jcb.org/cgi/doi/10.1083/jcb.200207030 JCB Article 41 Mitochondrial targeting and a novel transmembrane arrest of Alzheimer’s amyloid precursor protein impairs mitochondrial function in neuronal cells”
BackgroundInfluentialThe Alzheimer’s Disease Mitochondrial Cascade Hypothesis
Swerdlow, R. H., Burns, J. M., & Khan, S. M. (2010) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-100339 · Cited by 562 · see citing works
“Reduced AD subject cytochrome oxidase activity was first reported in 1990 [20].”
BackgroundBrain cytochrome oxidase in Alzheimer's disease
Kish, S. J., Bergeron, C., Rajput, A., Dozic, S., Mastrogiacomo, F., Chang, L., Wilson, J. M., DiStefano, L. M., & Nobrega, J. N. (1992) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1992.tb09439.x · Cited by 537 · see citing works
Estrogen: A master regulator of bioenergetic systems in the brain and body
Rettberg, J. R., Yao, J., & Brinton, R. D. (2014) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2013.08.001 · Cited by 534 · see citing works
“…brain tissue (Cottrell et al., 2001; Kish et al., 1992; Maurer et al., 2000; Mutisya et al., 1994; Parker et al., 1994b) as well as platelets (Bosetti et al., 2002; Cardoso et al., 2004; Parker et al., 1990, 1994a; Valla et al., 2006a) and fibroblasts (Curti et al., 1997) from AD patients.”
Mitochondrial DNA sequence variation in human evolution and disease.
Wallace, D. C. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.19.8739 · Cited by 520 · see citing works
Hashimoto, M., Rockenstein, E. M., Crews, L. A., & Masliah, E. (2003) · NeuroMolecular Medicine · doi:10.1385/nmm:4:1-2:21 · Cited by 498 · see citing works
Oxidative Stress in Neurodegenerative Diseases: From a Mitochondrial Point of View
Cenini, G., Lloret, A., & Cascella, R. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/2105607 · Cited by 435 · see citing works
“Studies performed in AD patients showed reduced cytochrome oxidase activity in platelets of AD subjects when compared to controls [74], and this mitochondrial defect was also demonstrated in the brain of AD patients [75].”
BackgroundOxidative stress: Free radical production in neural degeneration
Götz, M. E., Künig, G., Riederer, P. F., & Youdim, M. B. H. (1994) · Pharmacology & Therapeutics · doi:10.1016/0163-7258(94)90055-8 · Cited by 479 · see citing works
β‐Amyloid inhibits integrated mitochondrial respiration and key enzyme activities
Casley, C. S., Canevari, L., Land, J. M., Clark, J. B., & Sharpe, M. A. (2001) · Journal of Neurochemistry · doi:10.1046/j.0022-3042.2001.00681.x · Cited by 485 · see citing works
“Platelets from AD patients show reduced cytochrome oxidase activity despite having no interaction with amyloid plaques (Parker et al. 1990).”
BackgroundA selective defect of cytochrome c oxidase is present in brain of Alzheimer disease patients
Maurer, I. (2000) · Neurobiology of Aging · doi:10.1016/s0197-4580(00)00112-3 · Cited by 475 · see citing works
Amyloid toxicity in Alzheimer’s disease
Reiss, A. B., Arain, H. A., Stecker, M. M., Siegart, N. M., & Kasselman, L. J. (2018) · Reviews in the Neurosciences · doi:10.1515/revneuro-2017-0063 · Cited by 447 · see citing works
Perez Ortiz, J. M., & Swerdlow, R. H. (2019) · British Journal of Pharmacology · doi:10.1111/bph.14585 · Cited by 426 · see citing works
“These enzymes include (a) cytochrome c oxidase (COX; i.e., complex IV; Maurer, Zierz, & Möller, 2000; Mutisya, Bowling, & Beal, 1994; Parker et al., 1990), (b) pyruvate dehydrogenase complex (Gibson, Starkov, Blass, Rata, & Beal, 2010), and (c) the Krebs cycle α‐ ketoglutarate dehydrogenase complex (Gibson et al.”
BackgroundBrain Energy and Oxygen Metabolism: Emerging Role in Normal Function and Disease
Watts, M. E., Pocock, R., & Claudianos, C. (2018) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2018.00216 · Cited by 414 · see citing works
Reddy, P. H., Tripathi, R., Troung, Q., Tirumala, K., Reddy, T. P., Anekonda, V., Shirendeb, U. P., Calkins, M. J., Reddy, A. P., Mao, P., et al. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2011.10.011 · Cited by 394 · see citing works
Mitochondrial dysfunction in neurodegenerative disorders
Klemmensen, M. M., Borrowman, S. H., Pearce, C., Pyles, B., & Chandra, B. (2024) · Neurotherapeutics · doi:10.1016/j.neurot.2023.10.002 · Cited by 396 · see citing works
Cassarino, D. S., & Bennett, J. P. (1999) · Brain Research Reviews · doi:10.1016/s0165-0173(98)00046-0 · Cited by 379 · see citing works
Monzio Compagnoni, G., Di Fonzo, A., Corti, S., Comi, G. P., Bresolin, N., & Masliah, E. (2020) · Molecular Neurobiology · doi:10.1007/s12035-020-01926-1 · Cited by 378 · see citing works
“cytochrome oxidase activity (but not of other electron transport chain enzymes) in platelets of patients [27] and the same finding has been confirmed in an independent study detecting reduced ATP levels, increased reactive oxygen species, and decreased cytochrome oxidase activity (but normal cytochrome oxidase subunit…”
BackgroundHirano, M., & Pavlakis, S. G. (1994) · Journal of Child Neurology · doi:10.1177/088307389400900102 · Cited by 365 · see citing works
Bioenergetic and oxidative stress in neurodegenerative diseases
Bowling, A. C., & Beal, M. F. (1995) · Life Sciences · doi:10.1016/0024-3205(95)00055-b · Cited by 364 · see citing works
Are reactive oxygen species involved in Alzheimer's disease?
Benzi, G. (1995) · Neurobiology of Aging · doi:10.1016/0197-4580(95)00066-n · Cited by 365 · see citing works
Immunohistochemical evidence of oxidative [corrected] stress in Alzheimer's disease.
Pappolla, M. A., Omar, R. A., Kim, K. S., & Robakis, N. K. R. K. (1992) · PubMed Central · Cited by 363 · see citing works
Reddy, P. H. (2005) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2005.03530.x · Cited by 356 · see citing works
Bosetti, F. (2002) · Neurobiology of Aging · doi:10.1016/s0197-4580(01)00314-1 · Cited by 348 · see citing works
Manczak, M., & Reddy, P. H. (2012) · Human Molecular Genetics · doi:10.1093/hmg/dds360 · Cited by 348 · see citing works
Abnormalities of mitochondrial enzymes in Alzheimer disease
Gibson, G. E., Sheu, K.-F. R., & Blass, J. P. (1998) · Journal of Neural Transmission · doi:10.1007/s007020050099 · Cited by 345 · see citing works
“Deficiency of COX activity in platelets has been reported (Parker et al., 1990) and disputed (VanZuylen et al., 1992).”
BackgroundDavis, R. E., Miller, S., Herrnstadt, C., Ghosh, S. S., Fahy, E., Shinobu, L. A., Galasko, D., Thal, L. J., Beal, M. F., Howell, N., et al. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.9.4526 · Cited by 341 · see citing works
Self-citationRetractedOxidative stress in Alzheimer's disease
Chauhan, V. P. S., & Chauhan, A. (2006) · Pathophysiology · doi:10.1016/j.pathophys.2006.05.004 · Cited by 341 · see citing works
Cui, K., Luo, X., Xu, K., & Murthy, M. R. V. (2004) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2004.05.023 · Cited by 334 · see citing works
Cellular metabolic and autophagic pathways: Traffic control by redox signaling
Dodson, M. B., Darley-Usmar, V. M., & Zhang, J. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.05.014 · Cited by 325 · see citing works
Mitochondria, calcium and cell death: A deadly triad in neurodegeneration
Celsi, F., Pizzo, P., Brini, M., Leo, S., Fotino, C., Pinton, P., & Rizzuto, R. (2009) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2009.02.021 · Cited by 321 · see citing works
Mitochondrial Dysfunctions in Neurodegenerative Diseases: Relevance to Alzheimer’s Disease
Hroudová, J., Singh, N., & Fišar, Z. (2014) · BioMed Research International · doi:10.1155/2014/175062 · Cited by 319 · see citing works
“Volume 2014, Article ID 175062, 9 pages http://dx.doi.org/10.1155/2014/175062 in neurodegenerative process might affect mitochondrial parameters and also ATP production, membrane potential, permeability transition pore (MPTP) activation, and calcium uptake.”
BackgroundInfluentialAmyloid‐Beta Interaction with Mitochondria
Pagani, L., & Eckert, A. (2011) · International Journal of Alzheimer’s Disease · doi:10.4061/2011/925050 · Cited by 309 · see citing works
Brain aging, Alzheimer's disease, and mitochondria
Swerdlow, R. H. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2011.08.012 · Cited by 306 · see citing works
“In addition to the brain, reduced COX activity is also seen in AD subject platelets and fibroblasts [127, 128].”
BackgroundThe development of mitochondrial medicine.
Luft, R. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.19.8731 · Cited by 302 · see citing works
Mitochondrial dysfunction and oxidative stress in aging and neurodegenerative disease
Albers, D. S., & Beal, M. F. (2000) · Springer eBooks · doi:10.1007/978-3-7091-6781-6_16 · Cited by 297 · see citing works
Abnormal Mitochondrial Morphology in Sporadic Parkinson's and Alzheimer's Disease Cybrid Cell Lines
Trimmer, P. A., Swerdlow, R. H., Parks, J. K., Keeney, P. M., Bennett, J. P., Miller, S. W., Davis, R. E., & Parker, W. D. (2000) · Experimental Neurology · doi:10.1006/exnr.2000.7333 · Cited by 296 · see citing works
Self-citationAlzheimer’s disease: pathological mechanisms and the beneficial role of melatonin
Rosales‐Corral, S., Acuña-Castroviejo, D., Coto‐Montes, A. M., Boga, J. A., Manchester, L. C., Fuentes‐Broto, L., Korkmaz, A., Ma, S., Tan, D. X., & Reiter, R. J. (2011) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2011.00937.x · Cited by 293 · see citing works
“Likewise, AD as a primary defect in cytochrome oxidase was proposed years later [314].”
BackgroundAre mitochondria critical in the pathogenesis of Alzheimer's disease?
Reddy, P. H., & Beal, M. F. (2005) · Brain Research Reviews · doi:10.1016/j.brainresrev.2005.03.004 · Cited by 289 · see citing works
Oxidative damage and the Nrf2-ARE pathway in neurodegenerative diseases
Gan, L., & Johnson, J. A. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.12.011 · Cited by 288 · see citing works
Mitochondria and degenerative disorders
Orth, M., & Schapira, A. H. V. (2001) · American Journal of Medical Genetics · doi:10.1002/ajmg.1425 · Cited by 278 · see citing works
Cytochrome c oxidase is decreased in Alzheimer’s disease platelets
Cardoso, S. M., Proença, M. T., Santos, S., Santana, I., & Oliveira, C. R. (2004) · Neurobiology of Aging · doi:10.1016/s0197-4580(03)00033-2 · Cited by 281 · see citing works
“A previous study of AD platelet bioenergetics using crude homogenates failed to find a complex IV defect [33] while one study that assessed complex IV activity in purified mitochondrial fractions found an ∼50% defect [20].”
BackgroundResultInfluentialHarris, S. A., & Harris, E. A. (2015) · Journal of Alzheimer's Disease · doi:10.3233/jad-142853 · Cited by 279 · see citing works
Mechanisms of mitochondrial dysfunction and energy deficiency in Alzheimer’s disease
Atamna, H., & Frey, W. H. (2007) · Mitochondrion · doi:10.1016/j.mito.2007.06.001 · Cited by 278 · see citing works
Insulin Resistance and Alzheimer’s Disease: Bioenergetic Linkages
Neth, B. J., & Craft, S. (2017) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00345 · Cited by 275 · see citing works
“Reduced activity of complex IV, also known as cytochrome c oxidase (COX), has been widely reported in platelets as well as within the brain, which supports the view of AD being a systemic disorder (Parker et al., 1990; Cardoso et al., 2004).”
BackgroundMitochondrial Aspects of Synaptic Dysfunction in Alzheimer’s Disease
Cai, Q., & Tammineni, P. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-160726 · Cited by 274 · see citing works
“AD brains [76–84].”
Amyloid beta, mitochondrial structural and functional dynamics in Alzheimer's disease
Reddy, P. H. (2009) · Experimental Neurology · doi:10.1016/j.expneurol.2009.03.042 · Cited by 264 · see citing works
Mitophagy in Alzheimer’s Disease and Other Age-Related Neurodegenerative Diseases
Cai, Q., & Jeong, Y. Y. (2020) · Cells · doi:10.3390/cells9010150 · Cited by 263 · see citing works
Vitamin E and Alzheimer disease: the basis for additional clinical trials
Grundman, M. (2000) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/71.2.630s · Cited by 267 · see citing works
Mecocci, P., Boccardi, V., Cecchetti, R., Bastiani, P., Scamosci, M., Ruggiero, C., & Baroni, M. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-170732 · Cited by 256 · see citing works
“The fact that some mitochondrial defects observed in AD patients are not brain-limited, as shown by lower enzymatic activity, such as cytochrome oxidase, in mitochondria from peripheral cells (platelets and fibroblasts), strongly support the concept that AD is a systemic disease [31, 32].”
Sheehan, J. P., Swerdlow, R. H., Miller, S. W., Davis, R. E., Parks, J. K., Parker, W. D., & Tuttle, J. B. (1997) · The Journal of Neuroscience · doi:10.1523/jneurosci.17-12-04612.1997 · Cited by 249 · see citing works
Self-citationReich, N., & Hölscher, C. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.970925 · Cited by 248 · see citing works
Amyloid-β as a Modulator of Synaptic Plasticity
Parihar, M. S., & Brewer, G. J. (2010) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-101020 · Cited by 249 · see citing works
“ly stages of AD, there is already a reduction in the number of mitochondria [280] and the activities of tricarboxylic acid cycle enzymes [281] and COX [282].”
Bioenergetics and glutamate excitotoxicity
Greene, J. G., & Greenamyre, J. T. (1996) · Progress in Neurobiology · doi:10.1016/0301-0082(96)00006-8 · Cited by 246 · see citing works
Reddy, P. H., Mańczak, M., Mao, P., Calkins, M. J., Reddy, A. P., & Shirendeb, U. P. (2010) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-100504 · Cited by 240 · see citing works
“their platelets [78], in AD transgenic mice [34,37,38,”
Valla, J. E., Berndt, J. D., & Gonzalez-Lima, F. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-13-04923.2001 · Cited by 237 · see citing works
Holper, L., Ben‐Shachar, D., & Mann, J. (2018) · Neuropsychopharmacology · doi:10.1038/s41386-018-0090-0 · Cited by 234 · see citing works
Mitochondrial Medicine for Aging and Neurodegenerative Diseases
Reddy, P. H. (2008) · NeuroMolecular Medicine · doi:10.1007/s12017-008-8044-z · Cited by 230 · see citing works
“Decreased levels of mitochondrial enzymes––including pyruvate dehydrogenase complex, a-ketoglutarate dehydrogenase complex, and cytochrome oxidase––have been reported (Parker et al. 1990; Gibson et al. 1998).”
BackgroundLymphocyte oxidative DNA damage and plasma antioxidants in Alzheimer disease
Mecocci, P. (2002) · Archives of Neurology · doi:10.1001/archneur.59.5.794 · Cited by 229 · see citing works
Is Alzheimer’s disease a systemic disease?
Morris, J. K., Honea, R. A., Vidoni, E. D., Swerdlow, R. H., & Burns, J. M. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2014.04.012 · Cited by 219 · see citing works
Mitochondria as a Therapeutic Target for Aging and Neurodegenerative Diseases
Reddy, P. H., & Reddy, T. P. (2011) · Current Alzheimer Research · doi:10.2174/156720511795745401 · Cited by 227 · see citing works
Aleardi, A. M., Benard, G., Augereau, O., Malgat, M., Talbot, J.-C., Mazat, J., Letellier, T., Dachary-Prigent, J., Solaini, G., & Rossignol, R. (2005) · Journal of Bioenergetics and Biomembranes · doi:10.1007/s10863-005-6631-3 · Cited by 225 · see citing works
Mitochondrial dysfunction in schizophrenia: a possible linkage to dopamine
Ben-Shachar, D. (2002) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2002.01263.x · Cited by 232 · see citing works
Contributory mechanisms in the causation of neurodegenerative disorders
Lees, G. J. (1993) · Neuroscience · doi:10.1016/0306-4522(93)90254-d · Cited by 221 · see citing works
Dysfunctional Mitochondria and Mitophagy as Drivers of Alzheimer’s Disease Pathogenesis
Chakravorty, A., Jetto, C. T., & Manjithaya, R. R. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00311 · Cited by 219 · see citing works
Macdonald, R., Barnes, K., Hastings, C., & Mortiboys, H. (2018) · Biochemical Society Transactions · doi:10.1042/bst20170501 · Cited by 216 · see citing works
Mitochondrial membrane fluidity and oxidative damage to mitochondrial DNA in aged and AD human brain
Mecocci, P., Beal, M. F., Cecchetti, R., Polidori, M. C., Cherubini, A., Chionne, F., Avellini, L., Romano, G., & Senin, U. (1997) · Molecular and Chemical Neuropathology · doi:10.1007/bf02815160 · Cited by 215 · see citing works
Mitochondrial complex i subunits expression is altered in schizophrenia: a postmortem study
Karry, R., Klein, E., & Ben‐Shachar, D. (2004) · Biological Psychiatry · doi:10.1016/j.biopsych.2003.12.012 · Cited by 208 · see citing works
The Alzheimer's disease mitochondrial cascade hypothesis: an update
Swerdlow, R. H., & Khan, S. M. (2009) · Experimental Neurology · doi:10.1016/j.expneurol.2009.01.011 · Cited by 206 · see citing works
“The AD CO Vmax activity reduction was first shown in platelets in 1990 and brain in 1992 (Parker et al., 1990; Kish et al., 1992).”
BackgroundMitochondrial alterations Alzheimer's disease
Baloyannis, S. J., Costa, V., & Michmizos, D. (2004) · American Journal of Alzheimer's Disease & Other Dementias® · doi:10.1177/153331750401900205 · Cited by 206 · see citing works
Functional mitochondria are required for amyloid β‐mediated neurotoxicity
Cardoso, S. M., Santos, S., Swerdlow, R. H., & Oliveira, C. R. (2001) · The FASEB Journal · doi:10.1096/fj.00-0561fje · Cited by 203 · see citing works
“Other data suggest that bioenergetic failure resulting from depressed cytochrome c oxidase activity and reactive oxygen species (ROS) overproduction could contribute to neuronal death in AD (6, 7, 8).”
BackgroundSwerdlow, R. H. (2011) · Antioxidants and Redox Signaling · doi:10.1089/ars.2011.4149 · Cited by 203 · see citing works
“Apolipoprotein E4 (1-272) fragment is associ-”
BackgroundImpairment in mitochondrial cytochrome oxidase gene expression in Alzheimer disease.
Chandrasekaran, K., Giordano, T., Brady, D., Stoll, J., Martin, L. J., & Rapoport, S. (1994) · Brain Research. Molecular Brain Research · doi:10.1016/0169-328x(94)90147-3 · Cited by 221 · see citing works
Jiang, D., Men, L., Wang, J., Zhang, Y., Chickenyen, S., Wang, Y., & Zhou, F. (2007) · Biochemistry · doi:10.1021/bi700508n · Cited by 202 · see citing works
Emerging roles of pathogens in Alzheimer disease
Miklossy, J. (2011) · Expert Reviews in Molecular Medicine · doi:10.1017/s1462399411002006 · Cited by 199 · see citing works
“75) are also significant contributors to the pathogenesis of AD.”
BackgroundMitochondria in Neurodegeneration
Lezi, E., & Swerdlow, R. H. (2011) · Advances in experimental medicine and biology · doi:10.1007/978-94-007-2869-1_12 · Cited by 204 · see citing works
“A similar finding was made in AD brains in 1992 (Parker et al., 1990a; Kish et al., 1992).”
BackgroundResultPotential Therapeutic Benefits of Strategies Directed to Mitochondria
Camara, A. K. S., Lesnefsky, E. J., & Stowe, D. F. (2009) · Antioxidants and Redox Signaling · doi:10.1089/ars.2009.2788 · Cited by 195 · see citing works
“It is noteworthy that at an early stage of AD there is already a reduced number of mitochondria (247, 257), brain glucose metabolism is decreased (247, 287), and the activities of TCA cycle enzymes (79, 520) and cytochrome c oxidase are reduced (97, 247, 441) while there is enhanced cytochrome c release (177, 296), mP…”
BackgroundDragicevic, N., Mamcarz, M. B., Zhu, Y., Buzzeo, R. W., Tan, J., Arendash, G. W., & Bradshaw, P. C. (2010) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-100342 · Cited by 193 · see citing works
Mitochondrial genes are altered in blood early in Alzheimer's disease
Lunnon, K., Keohane, A., Pidsley, R., Newhouse, S., Riddoch-Contreras, J., Thubron, E. B., Devall, M., Soininen, H., Kłoszewska, I., Mecocci, P., et al. (2017) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2016.12.029 · Cited by 190 · see citing works
“…of oxidative damage in AD brain appear to be mirrored in the periphery including in platelets (Bosetti et al., 2002; Cardoso et al., 2004; Parker et al., 1990; Valla et al., 2006) and white blood cells from AD patients (Feldhaus et al., 2011; Lunnon et al., 2012, 2013; Mecocci et al.,…”
BackgroundMitochondrial Dysfunction in Aging and Alzheimer's Disease: Strategies to Protect Neurons
Reddy, P. H. (2007) · Antioxidants and Redox Signaling · doi:10.1089/ars.2007.1754 · Cited by 187 · see citing works
“Oxidative damage has been reported in aging and age-related neurodegenerative diseases, including AD (6, 22, 32, 45, 55, 58, 64, 81).”
- Authors
- Parker, W. D., Filley, C. M., & Parks, J. K.
- Affiliations
- University of Colorado Denver (US)
- Venue
- Neurology
- Published
- 1990-08
- Volume
- 40
- Issue
- 8
- Pages
- 1302-1302
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- OpenAlex
- W1988731658
- Cited by
- 598
- References
- 0
- Citations by year
- 2026: 19 · 2025: 10 · 2024: 12 · 2023: 20 · 2022: 9 · 2021: 22 · 2020: 25 · 2019: 19 · 2018: 18 · 2017: 18 · 2016: 28 · 2015: 10 · 2014: 10 · 2013: 21 · 2012: 15
- FWCI
- 7.27
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (7r01ns025382-06)
- National Institute of Neurological Disorders and Stroke (NS25382)
- National Center for Research Resources (RR-69)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- cytochrome oxidase deficiency, Alzheimer's disease, platelet mitochondria, electron transport chain, mitochondrial dysfunction, systemic disease
- MeSH terms
- Aged, Alzheimer Disease, Blood Platelets, Electron Transport Complex IV, Electron Transport, Female, Humans, Kinetics, Male, Mitochondria, Reference Values, Cytochrome-c Oxidase Deficiency
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
