Brain cytochrome oxidase in Alzheimer's disease
Abstract
A recent demonstration of markedly reduced (-50%) activity of cytochrome oxidase (CO; complex 4), the terminal enzyme of the mitochondrial enzyme transport chain, in platelets of patients with Alzheimer's disease (AD) suggested the possibility of a systemic and etiologically fundamental CO defect in AD. To determine whether a CO deficiency occurs in AD brain, we measured the activity of CO in homogenates of autopsied brain regions of 19 patients with AD and 30 controls matched with respect to age, postmortem time, sex, and, as indices of agonal status, brain pH and lactic acid concentration. Mean CO activity in AD brain was reduced in frontal (-26%: p less than 0.01), temporal (-17%; p less than 0.05), and parietal (-16%; not significant, p = 0.055) cortices. In occipital cortex and putamen, mean CO levels were normal, whereas in hippocampus, CO activity, on average, was nonsignificantly elevated (20%). The reduction of CO activity, which is tightly coupled to neuronal metabolic activity, could be explained by hypofunction of neurons, neuronal or mitochondrial loss, or possibly by a more primary, but region-specific, defect in the enzyme itself. The absence of a CO activity reduction in all of the examined brain areas does not support the notion of a generalized brain CO abnormality. Although the functional significance of a 16-26% cerebral cortical CO deficit in human brain is not known, a deficiency of this key energy-metabolizing enzyme could reduce energy stores and thereby contribute to the brain dysfunction and neurodegenerative processes in AD.
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Compelling evidence links neurodegeneration to altered brain metabolism and mitochondrial dysfunction, both of which are early hallmarks of Alzheimer's disease.
“Compelling evidence links neurodegeneration to altered brain metabolism and mitochondrial dysfunction, both of which are early hallmarks of AD [21–28].”
From Neuronal Apolipoprotein E4 Expression Results in Proteome-Wide Alterations and Compromises Bioenergetic Capacity by Disrupting Mitochondrial Function (2019) · cites this paper as [22]
COX activity is reduced in AD brain mitochondria.
“COX activity is also reduced in AD brain mitochondria [122, 126].”
From Brain aging, Alzheimer's disease, and mitochondria (2011) · cites this paper as [126]
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- Authors
- Kish, S. J., Bergeron, C., Rajput, A., Dozic, S., Mastrogiacomo, F., Chang, L., Wilson, J. M., DiStefano, L. M., & Nobrega, J. N.
- Affiliations
- University of Saskatchewan (CA)
- University of Belgrade (RS)
- Corresponding author
- Kish, Stephen J.
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 1992-08
- Volume
- 59
- Issue
- 2
- Pages
- 776-779
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W1985667235
- Cited by
- 537
- References
- 25
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 7 · 2023: 15 · 2022: 9 · 2021: 21 · 2020: 19 · 2019: 14 · 2018: 14 · 2017: 12 · 2016: 14 · 2015: 12 · 2014: 11 · 2013: 20 · 2012: 20
- FWCI
- 7.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (2r01ns026034-07)
- National Institute of Neurological Disorders and Stroke (NS26034)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, cytochrome c oxidase, mitochondrial electron transport chain, brain energy metabolism, frontal cortex, temporal cortex, parietal cortex, hippocampus, neuronal loss, neurodegeneration
- MeSH terms
- Aged, Alzheimer Disease, Autopsy, Brain, Electron Transport Complex IV, Female, Humans, Male
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