Evidence for brain glucose dysregulation in Alzheimer's disease

TLDR

The link between brain glucose dysregulation and Alzheimer’s disease pathogenesis remains uncertain. In an autopsy cohort, researchers measured brain glucose levels, glycolytic amino‑acid ratios, and neuronal (GLUT3) and astrocytic (GLUT1) transporter expression, and examined their association with pre‑mortem plasma glucose. Higher brain glucose, diminished glycolytic flux, and reduced GLUT3 correlate with AD severity and symptoms, and rising fasting plasma glucose predicts increased brain glucose, suggesting early intrinsic glucose dysregulation in AD.

Abstract

Abstract Introduction It is unclear whether abnormalities in brain glucose homeostasis are associated with Alzheimer's disease (AD) pathogenesis. Methods Within the autopsy cohort of the Baltimore Longitudinal Study of Aging, we measured brain glucose concentration and assessed the ratios of the glycolytic amino acids, serine, glycine, and alanine to glucose. We also quantified protein levels of the neuronal (GLUT3) and astrocytic (GLUT1) glucose transporters. Finally, we assessed the relationships between plasma glucose measured before death and brain tissue glucose. Results Higher brain tissue glucose concentration, reduced glycolytic flux, and lower GLUT3 are related to severity of AD pathology and the expression of AD symptoms. Longitudinal increases in fasting plasma glucose levels are associated with higher brain tissue glucose concentrations. Discussion Impaired glucose metabolism due to reduced glycolytic flux may be intrinsic to AD pathogenesis. Abnormalities in brain glucose homeostasis may begin several years before the onset of clinical symptoms.