Evidence for brain glucose dysregulation in Alzheimer's disease

Alzheimers Dement. 2018 Mar;14(3):318-329. doi: 10.1016/j.jalz.2017.09.011. Epub 2017 Oct 19.


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.

Keywords: Alzheimer's disease; GLUT1; GLUT3; Glucose; Glycolysis; Insulin resistance; Mass spectrometry; Neuritic plaque; Neurofibrillary tangles.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Baltimore
  • Brain / metabolism*
  • Brain / pathology
  • Female
  • Glucose / metabolism*
  • Glucose Transporter Type 1 / metabolism
  • Glucose Transporter Type 3 / metabolism
  • Humans
  • Longitudinal Studies
  • Male
  • Metabolomics
  • Middle Aged
  • Prospective Studies


  • Glucose Transporter Type 1
  • Glucose Transporter Type 3
  • SLC2A1 protein, human
  • SLC2A3 protein, human
  • Glucose