Evidence for brain glucose dysregulation in Alzheimer's disease

Yang An, Vijay R. Varma, Sudhir Varma, Ramon Casanova, Eric Dammer, Olga Pletnikova, Chee W. Chia, Josephine M. Egan, Luigi Ferrucci, Juan Troncoso, Allan I. Levey, James Lah, Nicholas T. Seyfried, Cristina Legido-Quigley, Richard O'Brien, Madhav Thambisetty

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)318-329
Number of pages12
JournalAlzheimer's and Dementia
Volume14
Issue number3
DOIs
StatePublished - Mar 2018

Keywords

  • Alzheimer's disease
  • GLUT1
  • GLUT3
  • Glucose
  • Glycolysis
  • Insulin resistance
  • Mass spectrometry
  • Neuritic plaque
  • Neurofibrillary tangles

ASJC Scopus subject areas

  • Epidemiology
  • Health Policy
  • Developmental Neuroscience
  • Clinical Neurology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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