An immunochemical study of the pyruvate dehydrogenase deficit in Alzheimer's disease brain.
Level 4 - case-series / case-control
Postmortem case-control study comparing enzyme activity and protein levels in human brain tissue
PubMed 4004169 · doi:10.1002/ana.410170505
What was done
Researchers measured the activity of the pyruvate dehydrogenase complex (PDHC) and glutamate dehydrogenase in postmortem frontal cortex (histologically affected) and occipital cortex (histologically unaffected) from patients with Alzheimer's disease and controls. They evaluated potential confounders including donor age, postmortem interval, and enzyme inactivation upon homogenate incubation. They also conducted immunochemical inhibition assays and immunoblots using antibodies against purified bovine PDHC to determine whether the deficit was due to altered enzyme structure or reduced protein quantity.
What was found
PDHC activity was reduced to approximately 30% of control values in both histologically affected frontal cortex and histologically unaffected occipital cortex in Alzheimer's disease brains. Glutamate dehydrogenase activity was normal. Enzyme activity showed no significant correlation with donor age or postmortem delay, and incubation with brain homogenates did not significantly inactivate PDHC. Antibodies against bovine PDHC inhibited Alzheimer and control PDHC equally per unit of enzyme activity, and immunoblots showed no antigenic differences between groups; however, the antibody inhibited Alzheimer PDHC more effectively per milligram of protein, indicating a reduced quantity of normal PDHC protein.
Why it matters
This study demonstrates that the metabolic deficit in pyruvate dehydrogenase complex in Alzheimer's disease is widespread across cortical regions and results from a reduction in normal enzyme protein rather than structural mutation or postmortem degradation.
Limits
The abstract does not report sample sizes for patients or controls. As a postmortem tissue study, unmeasured agonal states or perimortem factors cannot be excluded, and clinical disease severity was not detailed.
Cited by
- supports Pyruvate dehydrogenase complex activity is deficient in neurodegenerative conditions such as Alzheimer's disease.