Lower GLUT1 and unchanged MCT1 in Alzheimer's disease cerebrovasculature.
Level 4 - case-series / case-control
Post-mortem human case-control study using brain tissue
PubMed 38441044 · doi:10.1177/0271678X241237484
What was done
Researchers measured protein levels of glucose transporter-1 (GLUT1) and monocarboxylate transporter-1 (MCT1) using Western immunoblotting in microvessel extracts from the parietal cortex of 60 deceased participants in the Religious Orders Study. They evaluated differences between participants with and without a clinical diagnosis of Alzheimer's disease (AD) and tested for associations with cognitive scores, neuropathological markers (Aβ, tau, neuritic plaques, cerebrovascular β-secretase-derived fragments), sex, age at death, and APOE-ε4 genotype.
What was found
No numerical values or effect sizes were reported in the abstract. Directionally, participants with clinically diagnosed AD had significantly lower cerebrovascular GLUT1 levels, whereas MCT1 levels were unchanged. Lower GLUT1 was associated with lower cognitive scores and was inversely correlated with neuritic plaques and cerebrovascular β-secretase-derived fragments. MCT1 had no association with cognitive scores. Neither transporter was significantly associated with other Aβ or tau markers, sex, age at death, or APOE-ε4 status.
Why it matters
These findings suggest that impaired blood-brain barrier glucose transport in AD occurs alongside preserved ketone body transport capacity. This provides mechanistic support for investigating ketogenic therapies as alternative energy sources for the brain in AD.
Limits
This is a post-mortem, cross-sectional observational study, so it cannot establish causality or determine if GLUT1 reduction precedes or results from AD pathology. The sample size was modest (n = 60), measurements were restricted to a single brain region (parietal cortex), and the abstract provides no numerical data, confidence intervals, or p-values. In vitro protein abundance does not directly confirm in vivo transport kinetics.
Cited by
- supports GLUT1 is the primary glucose transporter at the blood-brain barrier and is significantly reduced in postmortem brain vessels of Alzheimer's patients.