Decreased pyruvate dehydrogenase complex activity in Huntington and Alzheimer brain.
Level 4 - case-series / case-control
Postmortem human tissue and laboratory cell comparative case-control study
PubMed 6219611 · doi:10.1002/ana.410130116
What was done
The authors measured the enzymatic activities of the pyruvate dehydrogenase complex (PDHC), choline acetyltransferase (CAT), and the mitochondrial marker fumarase in postmortem brain regions (caudate, putamen, hippocampus, frontal cortex, and amygdala) from patients with Huntington disease and Alzheimer disease. They also evaluated total PDHC activity and activation in cultured skin fibroblasts from four patients with trisomy 21 (Down syndrome), as well as fibroblasts from patients with Huntington disease and Alzheimer disease.
What was found
The abstract reports no numerical values, standard deviations, or p-values. PDHC activity was decreased in Huntington-affected regions (caudate, putamen, and hippocampus) and Alzheimer-affected regions (frontal cortex). CAT activity was reduced in caudate, putamen, and frontal cortex, but was preserved in the Huntington hippocampus. Fumarase activity was normal across all analyzed brain regions. PDHC and CAT activities correlated in the caudate, putamen, and amygdala, but not in the hippocampus or frontal cortex. In cultured fibroblasts, total activity and activation of PDHC were reduced in four patients with Down syndrome, whereas no PDHC abnormalities were detected in Huntington or Alzheimer fibroblasts.
Why it matters
The findings demonstrate localized impairment of cerebral glucose oxidative metabolism via PDHC deficiency in neurodegenerative disease brain tissue without evidence of an intrinsic systemic defect in peripheral fibroblasts from Huntington or Alzheimer patients.
Limits
The abstract does not state the sample sizes for the postmortem brain tissue cohorts, nor does it provide exact quantitative enzyme measurements, variance estimates, or formal statistical test results. Postmortem brain tissue analyses are susceptible to confounding by agonal state, postmortem interval, and tissue handling artifacts.
Cited by
- supports Pyruvate dehydrogenase complex activity is deficient in neurodegenerative conditions such as Alzheimer's disease.