GLUT1 reductions exacerbate Alzheimer's disease vasculo-neuronal dysfunction and degeneration

Nat Neurosci. 2015 Apr;18(4):521-530. doi: 10.1038/nn.3966. Epub 2015 Mar 2.


The glucose transporter GLUT1 at the blood-brain barrier (BBB) mediates glucose transport into the brain. Alzheimer's disease is characterized by early reductions in glucose transport associated with diminished GLUT1 expression at the BBB. Whether GLUT1 reduction influences disease pathogenesis remains, however, elusive. Here we show that GLUT1 deficiency in mice overexpressing amyloid β-peptide (Aβ) precursor protein leads to early cerebral microvascular degeneration, blood flow reductions and dysregulation and BBB breakdown, and to accelerated amyloid β-peptide (Aβ) pathology, reduced Aβ clearance, diminished neuronal activity, behavioral deficits, and progressive neuronal loss and neurodegeneration that develop after initial cerebrovascular degenerative changes. We also show that GLUT1 deficiency in endothelium, but not in astrocytes, initiates the vascular phenotype as shown by BBB breakdown. Thus, reduced BBB GLUT1 expression worsens Alzheimer's disease cerebrovascular degeneration, neuropathology and cognitive function, suggesting that GLUT1 may represent a therapeutic target for Alzheimer's disease vasculo-neuronal dysfunction and degeneration.

Publication types

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

MeSH terms

  • Alzheimer Disease* / metabolism
  • Alzheimer Disease* / pathology
  • Alzheimer Disease* / physiopathology
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Blood-Brain Barrier* / metabolism
  • Blood-Brain Barrier* / pathology
  • Blood-Brain Barrier* / physiopathology
  • Cerebrovascular Circulation / physiology*
  • Disease Models, Animal
  • Endothelium, Vascular* / metabolism
  • Endothelium, Vascular* / pathology
  • Endothelium, Vascular* / physiopathology
  • Glucose Transporter Type 1 / deficiency*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic


  • Amyloid beta-Peptides
  • Glucose Transporter Type 1