“The brain is the most energy-demanding organ of the body and is critically dependent on a daily supply of a quarter of a pound of glucose, its main energy source, to generate the ATP it needs to function.”

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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 Winkler and colleagues 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, as well as accelerated amyloid β-peptide (Aβ) pathology, reduced Aβ clearance, diminished neuronal activity and  behavioral deficits. Progressive neuronal loss and neurodegeneration developed after initial cerebrovascular degenerative changes.

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They demonstrate 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. The authors suggest that GLUT1 may represent a therapeutic target for Alzheimer’s disease vasculo-neuronal dysfunction and degeneration.
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Winkler EA, Nishida Y, Sagare AP, Rege SV, Bell RD, Perlmutter D, Sengillo JD, Hillman S, Kong P, Nelson AR, Sullivan JS, Zhao Z, Meiselman HJ, Wenby RB, Soto J, Abel ED, Makshanoff J, Zuniga E, De Vivo DC and Zlokovic BV: GLUT1 reductions exacerbate Alzheimer’s disease vasculo-neuronal dysfunction and degeneration. Nature Neuroscience 18(4): 521-530 (2015).
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http://www.ncbi.nlm.nih.gov/pubmed/25730668