Cytochrome c oxidase and mitochondrial F1F0-ATPase (ATP synthase) activities in platelets and brain from patients with Alzheimer's disease.
Evidence suggests that mitochondrial dysfunction is prominent in Alzheimer's disease (AD). A failure of one or more of the mitochondrial electron transport chain enzymes or of F(1)F(0)-ATPase (ATP synthase) could compromise brain energy stores, generate damaging reactive oxygen species (ROS), and lead to neuronal death. In the present study, cytochrome c oxidase (COX) and F(1)F(0)-ATPase activities of isolated mitochondria from platelets and postmortem motor cortex and hippocampus from AD patients and age-matched control subjects were assayed. Compared with controls, COX activity was decreased significantly in platelets (-30%, P < 0.01, n = 20) and hippocampus (-35 to -40%, P < 0.05, n = 6), but not in motor cortex from the AD patients. In contrast, in AD platelets and brain tissues, F(1)F(0)-ATP hydrolysis activity was not significantly changed. Moreover, the ATP synthesis rate was similar in mitochondria of platelets from AD patients and controls. These results demonstrate that COX but not F(1)F(0)-ATPase is a mitochondrial target in AD, in both a brain association area and in platelets. A reduced COX activity may make the tissue vulnerable to excitotoxicity or reduced oxygen availability.
Bosetti
Francesca
F
Scuola Superiore di Studi Universitari e di Perfezionamento S. Anna, Via G. Carducci 40, 56127 Pisa, Italy.
Brizzi
Francesca
F
Barogi
Silvia
S
Mancuso
Michelangelo
M
Siciliano
Gabriele
G
Tendi
Elisabetta A
EA
Murri
Luigi
L
Rapoport
Stanley I
SI
Solaini
Giancarlo
G
D000255:Adenosine Triphosphate / Q000096:biosynthesis / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000201:enzymology* / Q000473:pathology; D001792:Blood Platelets / Q000201:enzymology* / Q000378:metabolism; D001921:Brain / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D003576:Electron Transport Complex IV / Q000378:metabolism*; D005260:Female; D006801:Humans; D006868:Hydrolysis; D008297:Male; D008875:Middle Aged; D025261:Mitochondrial Proton-Translocating ATPases / Q000378:metabolism*
D000255:Adenosine Triphosphate; D003576:Electron Transport Complex IV; D025261:Mitochondrial Proton-Translocating ATPases