Cytochrome Oxidase Inhibition In Alzheimer’s Disease

  • F. Gonzalez-Lima
  • J. Valla
  • L. Jorandby


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.


Electron Transport Chain Cytochrome Oxidase Inferior Colliculus Estrogen Replacement Therapy Free Radical Production 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Springer Science+Business Media New York 1998

Authors and Affiliations

  • F. Gonzalez-Lima
    • 1
  • J. Valla
    • 1
  • L. Jorandby
    • 1
  1. 1.Institute for Neuroscience and Department of PsychologyThe University of Texas at AustinAustinUSA

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