Yang An1, Vijay R Varma2, Sudhir Varma3, Ramon Casanova4, Eric Dammer5, Olga Pletnikova6, Chee W Chia7, Josephine M Egan8, Luigi Ferrucci9, Juan Troncoso10, Allan I Levey11, James Lah11, Nicholas T Seyfried5, Cristina Legido-Quigley12, Richard O'Brien13, Madhav Thambisetty14. 1. Laboratory of Behavioral Neuroscience, National Institute on Aging (NIA), National Institutes of Health (NIH), Baltimore, MD, USA. 2. Clinical and Translational Neuroscience Unit, Laboratory of Behavioral Neuroscience, National Institute on Aging (NIA), National Institutes of Health (NIH), Baltimore, MD, USA. 3. HiThru Analytics, Laurel, MD, USA. 4. Department of Biostatistical Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, USA. 5. Department of Biochemistry, Emory University School of Medicine, Atlanta, GA, USA. 6. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. 7. Translational Research and Medical Services Section, National Institute on Aging (NIA), National Institutes of Health (NIH), Baltimore, MD, USA. 8. Laboratory of Clinical Investigation, National Institute on Aging (NIA), National Institutes of Health (NIH), Baltimore, MD, USA. 9. Longitudinal Studies Section, National Institute on Aging (NIA), National Institutes of Health (NIH), Baltimore, MD, USA. 10. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. 11. Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA. 12. Institute of Pharmaceutical Science, Kings College London, London, United Kingdom. 13. Department of Neurology, Duke University School of Medicine, Durham, NC, USA. 14. Clinical and Translational Neuroscience Unit, Laboratory of Behavioral Neuroscience, National Institute on Aging (NIA), National Institutes of Health (NIH), Baltimore, MD, USA. Electronic address: thambisettym@mail.nih.gov.
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.
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.
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