title: Mitochondrial Respiration in the Platelets of Patients with Alzheimer's Disease.
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.
authors.affiliation: Department of Psychiatry, First Faculty of Medicine, Charles University in Prague, Ke Karlovu 11, 120 00 Prague 2, Czech Republic.. zfisar@lf1.cuni.cz.
authors.forename: Zdeněk
authors.initials: Z
authors.lastname: Fišar
authors.forename: Jana
authors.initials: J
authors.lastname: Hroudová
authors.forename: Hana
authors.initials: H
authors.lastname: Hansíková
authors.forename: Jana
authors.initials: J
authors.lastname: Spáčilová
authors.forename: Petra
authors.initials: P
authors.lastname: Lelková
authors.forename: László
authors.initials: L
authors.lastname: Wenchich
authors.forename: Roman
authors.initials: R
authors.lastname: Jirák
authors.forename: Martina
authors.initials: M
authors.lastname: Zvěřová
authors.forename: Jiří
authors.initials: J
authors.lastname: Zeman
authors.forename: Pavel
authors.initials: P
authors.lastname: Martásek
authors.forename: Jiří
authors.initials: J
authors.lastname: Raboch
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D001057:Apolipoproteins E / Q000235:genetics; D015415:Biomarkers / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism*; D002950:Citrate (si)-Synthase / Q000378:metabolism; D042967:Electron Transport Complex I / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism*; D011110:Polymorphism, Genetic; D012372:ROC Curve; D014451:Ubiquinone / Q000031:analogs & derivatives / Q000097:blood
chemical_list: D001057:Apolipoproteins E; D015415:Biomarkers; D014451:Ubiquinone; D003576:Electron Transport Complex IV; D002950:Citrate (si)-Synthase; D042967:Electron Transport Complex I; C024989:coenzyme Q10