Brain cytochrome oxidase in Alzheimer's disease.
A recent demonstration of markedly reduced (-50%) activity of cytochrome oxidase (CO; complex 4), the terminal enzyme of the mitochondrial enzyme transport chain, in platelets of patients with Alzheimer's disease (AD) suggested the possibility of a systemic and etiologically fundamental CO defect in AD. To determine whether a CO deficiency occurs in AD brain, we measured the activity of CO in homogenates of autopsied brain regions of 19 patients with AD and 30 controls matched with respect to age, postmortem time, sex, and, as indices of agonal status, brain pH and lactic acid concentration. Mean CO activity in AD brain was reduced in frontal (-26%: p less than 0.01), temporal (-17%; p less than 0.05), and parietal (-16%; not significant, p = 0.055) cortices. In occipital cortex and putamen, mean CO levels were normal, whereas in hippocampus, CO activity, on average, was nonsignificantly elevated (20%). The reduction of CO activity, which is tightly coupled to neuronal metabolic activity, could be explained by hypofunction of neurons, neuronal or mitochondrial loss, or possibly by a more primary, but region-specific, defect in the enzyme itself. The absence of a CO activity reduction in all of the examined brain areas does not support the notion of a generalized brain CO abnormality. Although the functional significance of a 16-26% cerebral cortical CO deficit in human brain is not known, a deficiency of this key energy-metabolizing enzyme could reduce energy stores and thereby contribute to the brain dysfunction and neurodegenerative processes in AD.
Kish
S J
SJ
Human Neurochemical Pathology Laboratory, Clarke Institute of Psychiatry, Toronto, Ontario, Canada.
Bergeron
C
C
Rajput
A
A
Dozic
S
S
Mastrogiacomo
F
F
Chang
L J
LJ
Wilson
J M
JM
DiStefano
L M
LM
Nobrega
J N
JN
D000368:Aged; D000544:Alzheimer Disease / Q000201:enzymology*; D001344:Autopsy; D001921:Brain / Q000201:enzymology*; D003576:Electron Transport Complex IV / Q000032:analysis*; D005260:Female; D006801:Humans; D008297:Male
D003576:Electron Transport Complex IV