Coenzyme A-Dependent Tricarboxylic Acid Cycle Enzymes Are Decreased in Alzheimer's Disease Consistent With Cerebral Pantothenate Deficiency.
Level 4 - case-series / case-control
Case-control post-mortem human brain tissue study
PubMed 35754968 · doi:10.3389/fnagi.2022.893159
What was done
Proteomic analysis was conducted on post-mortem tissue from six functionally distinct brain regions in 9 sporadic Alzheimer's disease cases and 9 controls (total n = 18). The authors measured 33 cerebral proteins comprising the nine enzymes of the mitochondrial tricarboxylic acid (TCA) cycle and their cytoplasmic homologues to evaluate whether cerebral pantothenate deficiency disrupts coenzyme A (CoA)-dependent metabolic pathways.
What was found
Widespread protein alterations in sporadic Alzheimer's disease cases selectively affected two multi-subunit enzymes and two enzyme complexes modulated directly or indirectly by CoA: pyruvate dehydrogenase complex, isocitrate dehydrogenase, 2-oxoglutarate dehydrogenase complex, and succinyl-CoA synthetase. Exact quantitative effect sizes, protein concentrations, and p-values were not provided in the abstract.
Why it matters
These findings suggest that previously observed cerebral pantothenate (vitamin B5) deficiency in Alzheimer's disease may contribute to impaired brain energy metabolism specifically by depressing CoA-dependent TCA-cycle enzymes.
Limits
The sample size is very small (9 cases and 9 controls). The cross-sectional, post-mortem design precludes establishing causal directionality or tracking metabolic changes over the course of disease progression. Quantitative enzyme activity and exact protein level statistics are absent from the abstract.
Cited by
- supports Pyruvate dehydrogenase complex activity is deficient in neurodegenerative conditions such as Alzheimer's disease.