Cited by 345Alzheimer's disease research and treatmentsMitochondrial Function and PathologyBiochemical Acid Research Studies

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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

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Abstract

Abundant evidence, including critical information gathered by Prof. Siegfried Hoyer and his colleagues, indicates that abnormalities of cerebral metabolism are common in neurodegenerative diseases, including Alzheimer's Disease (AD). Alterations in mitochondrial enzymes likely underlie these deficits. Replicable reductions in AD brain occur in the pyruvate dehydrogenase complex (the link of glycolysis to the Kreb's cycle), the alpha-ketoglutarate dehydrogenase complex (KGDHC; the link of Kreb's cycle to glutamate metabolism) and cytochrome oxidase (the link of the Kreb's cycle to oxygen utilization). Available evidence suggests that deficiencies in KGDHC may be genetic in some cases, whereas evidence that the other two enzyme systems have a genetic component is lacking. Additional results indicate that the reductions can also be secondary to other causes including oxidative stress. A variety of data suggest that the mitochondrial insufficiencies contribute significantly to the pathophysiology of AD.

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Oxidative stress and mitochondrial dysfunction in Alzheimer’s disease
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Authors: Gibson, G. E., Sheu, K.-F. R., & Blass, J. P.
Affiliations: Cornell University (US)
ORCID: Gibson, G. E.
Venue: Journal of Neural Transmission
Publisher: Springer Science and Business Media LLC
Published: 1998-11-04
Volume: 105
Issue: 8-9
Pages: 855-870
ISSN: 0300-9564 (ISSN-L)
1435-1463
DOI: 10.1007/s007020050099
OpenAlex: W1989462226
Cited by: 345
References: 59
Citations by year: 2026: 6 · 2025: 7 · 2024: 7 · 2023: 14 · 2022: 14 · 2021: 12 · 2020: 20 · 2019: 12 · 2018: 11 · 2017: 15 · 2016: 23 · 2015: 19 · 2014: 7 · 2013: 14 · 2012: 12
FWCI: 4.29
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Journal of Neural Transmission (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5r35ag009014-07)
National Institute on Aging (AG11921, AG 09014, R01AG014600, R01AG011921, AG-14600)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Biochemical Acid Research Studies
Keywords: Alzheimer's disease, mitochondrial enzymes, pyruvate dehydrogenase complex, alpha-ketoglutarate dehydrogenase complex, cytochrome c oxidase, brain metabolism, neurodegeneration, oxidative stress, TCA cycle, glutamate metabolism, genetic deficiency
MeSH terms: Alzheimer Disease, Electron Transport Complex IV, Humans, Ketoglutarate Dehydrogenase Complex, Mitochondria, Pyruvate Dehydrogenase Complex, Oxidative Stress

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Abnormalities of mitochondrial enzymes in Alzheimer disease

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