D-Glucose uptake and clearance in the tauopathy Alzheimer's disease mouse brain detected by on-resonance variable delay multiple pulse MRI

J Cereb Blood Flow Metab. 2021 May;41(5):1013-1025. doi: 10.1177/0271678X20941264. Epub 2020 Jul 16.

Abstract

In this study, we applied on-resonance variable delay multiple pulse (onVDMP) MRI to study D-glucose uptake in a mouse model of Alzheimer's disease (AD) tauopathy and demonstrated its feasibility in discriminating AD mice from wild-type mice. The D-glucose uptake in the cortex of AD mice (1.70 ± 1.33%) was significantly reduced compared to that of wild-type mice (5.42 ± 0.70%, p = 0.0051). Also, a slower D-glucose uptake rate was found in the cerebrospinal fluid (CSF) of AD mice (0.08 ± 0.01 min-1) compared to their wild-type counterpart (0.56 ± 0.1 min-1, p < 0.001), which suggests the presence of an impaired glucose transporter on both blood-brain and blood-CSF barriers of these AD mice. Clearance of D-glucose was observed in the CSF of wild-type mice but not AD mice, which suggests dysfunction of the glymphatic system in the AD mice. The results in this study indicate that onVDMP MRI could be a cost-effective and widely available method for simultaneously evaluating glucose transporter and glymphatic function of AD. This study also suggests that tau protein affects the D-glucose uptake and glymphatic impairment in AD at a time point preceding neurofibrillary tangle pathology.

Keywords: Alzheimer’s diseases; Glucose uptake; chemical exchange saturation transfer; dynamic glucose enhanced; on-resonance variable delay multiple pulse; tau pathology.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Alzheimer Disease / diagnostic imaging*
  • Alzheimer Disease / metabolism*
  • Animals
  • Blood-Brain Barrier / metabolism
  • Brain / diagnostic imaging
  • Brain / metabolism*
  • Carbohydrate Metabolism, Inborn Errors / diagnosis
  • Carbohydrate Metabolism, Inborn Errors / metabolism*
  • Carbohydrate Metabolism, Inborn Errors / physiopathology
  • Cost-Benefit Analysis
  • Disease Models, Animal
  • Feasibility Studies
  • Female
  • Glucose / cerebrospinal fluid
  • Glucose / metabolism*
  • Glymphatic System / metabolism
  • Glymphatic System / physiopathology
  • Magnetic Resonance Imaging / economics
  • Magnetic Resonance Imaging / methods*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Monosaccharide Transport Proteins / deficiency*
  • Monosaccharide Transport Proteins / metabolism
  • Sensitivity and Specificity
  • Tauopathies / metabolism*
  • Tauopathies / pathology
  • tau Proteins / metabolism

Substances

  • Monosaccharide Transport Proteins
  • tau Proteins
  • Glucose

Supplementary concepts

  • Glut1 Deficiency Syndrome