Abstract
Mitochondrial dysfunctions significantly contribute to the pathogenesis of Alzheimer’s disease (AD). Here, we studied the relationship between AD and changes in the mitochondrial rates of respiration in blood platelets, respiratory chain complexes activity, and coenzyme Q10 plasma concentrations. In intact platelets obtained from AD patients, we observed a decrease in endogenous basal respiration rates, a decrease in the maximal capacity of the electron transport system (ETS), and higher respiratory rates after inhibiting complex I of the ETS. When normalized for citrate synthase activity, rotenone inhibited respiratory rates and complex I activity was significantly altered. In permeabilized platelets, mitochondrial respiration was completely rescued by the addition of complex I substrates. The changes in mitochondrial respiratory parameters were not associated with the progression of AD except for the capacity of the ETS in permeabilized platelets. In AD, complex I activity was increased, complex IV activity was decreased, and coenzyme Q10 plasma concentrations were decreased. Our data indicate that both insufficiency in substrates entering into the oxidative phosphorylation system and functional disturbances in the ETS complex are responsible for the decrease in respiration observed in intact platelets in AD patients. Analyses of complex IV activity, the respiratory rates of intact platelets, and the capacity of the ETS in permeabilized platelets may enable the characterization of mitochondrial dysfunctions in the initial stage of AD.
Keywords: Alzheimer’s disease, biomarker, mitochondrion, platelet, respiratory chain, respiratory rate.
Current Alzheimer Research
Title:Mitochondrial Respiration in the Platelets of Patients with Alzheimer’s Disease
Volume: 13 Issue: 8
Author(s): Zdeněk Fišar, Jana Hroudová, Hana Hansíková, Jana Spáčilová, Petra Lelková, László Wenchich, Roman Jirák, Martina Zvěřová, Jiří Zeman, Pavel Martásek and Jiří Raboch
Affiliation:
Keywords: Alzheimer’s disease, biomarker, mitochondrion, platelet, respiratory chain, respiratory rate.
Abstract: Mitochondrial dysfunctions significantly contribute to the pathogenesis of Alzheimer’s disease (AD). Here, we studied the relationship between AD and changes in the mitochondrial rates of respiration in blood platelets, respiratory chain complexes activity, and coenzyme Q10 plasma concentrations. In intact platelets obtained from AD patients, we observed a decrease in endogenous basal respiration rates, a decrease in the maximal capacity of the electron transport system (ETS), and higher respiratory rates after inhibiting complex I of the ETS. When normalized for citrate synthase activity, rotenone inhibited respiratory rates and complex I activity was significantly altered. In permeabilized platelets, mitochondrial respiration was completely rescued by the addition of complex I substrates. The changes in mitochondrial respiratory parameters were not associated with the progression of AD except for the capacity of the ETS in permeabilized platelets. In AD, complex I activity was increased, complex IV activity was decreased, and coenzyme Q10 plasma concentrations were decreased. Our data indicate that both insufficiency in substrates entering into the oxidative phosphorylation system and functional disturbances in the ETS complex are responsible for the decrease in respiration observed in intact platelets in AD patients. Analyses of complex IV activity, the respiratory rates of intact platelets, and the capacity of the ETS in permeabilized platelets may enable the characterization of mitochondrial dysfunctions in the initial stage of AD.
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Fišar Zdeněk, Hroudová Jana, Hansíková Hana, Spáčilová Jana, Lelková Petra, Wenchich László, Jirák Roman, Zvěřová Martina, Zeman Jiří, Martásek Pavel and Raboch Jiří, Mitochondrial Respiration in the Platelets of Patients with Alzheimer’s Disease, Current Alzheimer Research 2016; 13 (8) . https://dx.doi.org/10.2174/1567205013666160314150856
DOI https://dx.doi.org/10.2174/1567205013666160314150856 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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