Analysis of the genes coding for subunit 10 and 15 of cytochrome c oxidase in Alzheimer's disease.
Decay of mitochondria and oxidative stress are associated with normal aging, but many neurodegenerative diseases, and particularly Alzheimer's disease (AD), are characterized by a significant increase in the intensity of these traits. Recent data suggest the possible contribution of heme deficiency to the progressive derangement of mitochondria in AD brain; shortage of heme, and particularly of heme-a, actually leads to loss of mitochondrial cytochrome c oxidase (COX), abnormal production of reactive oxygen species and altered amyloid precursor protein metabolism. We reasoned that differences in the amount and/or functioning of COX assembly subunit 10 (COX10) and 15 (COX15), the key enzymes involved in heme-a biosynthesis, could be linked to variations of the individual risk to develop AD. We analyzed their mRNA expression in the hippocampus from AD patients and controls, investigated the existence of nucleotide variations in their DNA sequences and analyzed their distribution in large groups of AD and control individuals. COX 15 mRNA was significantly more abundant in the cerebral tissue of AD patients (3.18 +/- 1.70 vs. 1.22 +/- 0.66 microg, normalized dose, P = 0.01). The IVS-178G>A SNP in COX10 and the c+1120C>T SNP in COX15 were significantly less represented in the patient group (P < 0.001 and P = 0.017, respectively) with respective odd ratios of 0.22 and 0.59, suggesting a possible protective role toward the risk for AD.
Vitali
Massimiliano
M
Section of Biochemistry, Faculty of Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, Italy.
Venturelli
Eliana
E
Galimberti
Daniela
D
Benerini Gatta
Luisa
L
Scarpini
Elio
E
Finazzi
Dario
D
D000368:Aged; D019883:Alkyl and Aryl Transferases / Q000235:genetics* / Q000378:metabolism*; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism*; D053327:Apolipoprotein E4 / Q000235:genetics; D003576:Electron Transport Complex IV / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D009483:Neuropsychological Tests; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D012737:Sex Factors
D053327:Apolipoprotein E4; D008565:Membrane Proteins; D012333:RNA, Messenger; C490115:COX10 protein, human; C548296:COX15 protein, human; D003576:Electron Transport Complex IV; D019883:Alkyl and Aryl Transferases