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 lg,
normalized dose, P = 0.01). The IVS-178G[A SNP in
COX10 and the c1120C[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.