Evidence for brain glucose dysregulation in Alzheimer's disease.
Level 4 - case-series / case-control
Postmortem cross-sectional tissue analysis linked to a prospective cohort
PubMed 29055815 · doi:10.1016/j.jalz.2017.09.011
What was done
Using postmortem tissue from the Baltimore Longitudinal Study of Aging autopsy cohort, researchers measured brain glucose concentrations, calculated ratios of glycolytic amino acids (serine, glycine, and alanine) to glucose to estimate glycolytic flux, and quantified protein levels of glucose transporters GLUT1 (astrocytic) and GLUT3 (neuronal). They also evaluated the relationship between longitudinal fasting plasma glucose measured prior to death and postmortem brain tissue glucose.
What was found
The abstract reports directional associations without quantitative metrics or effect sizes. Higher brain tissue glucose concentration, reduced glycolytic flux, and lower GLUT3 levels were associated with greater severity of Alzheimer's disease pathology and clinical symptom expression. In addition, longitudinal increases in premortem fasting plasma glucose were associated with higher postmortem brain tissue glucose concentrations.
Why it matters
These findings suggest that impaired cerebral glycolysis and altered glucose transport may be directly involved in Alzheimer's pathogenesis and linked to systemic glucose dysregulation years before clinical diagnosis.
Limits
The abstract provides no sample size (n is unspecified), numerical values, effect sizes, or confidence intervals. The postmortem cross-sectional design cannot establish causality between glucose dysregulation and neurodegeneration, and findings from an autopsy cohort may be subject to survival and selection biases.
Cited by
- supports In early Alzheimer's disease, there is more glucose present in the brain than in control groups, but the brain is unable to use it.