GLUT1 reductions exacerbate Alzheimer's disease vasculo-neuronal dysfunction and
Authors 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, Zlokovic BV
Submitted By Submitted Externally on 5/5/2015
Status Published
Journal Nature neuroscience
Year 2015
Date Published 4/1/2015
Volume : Pages 18 : 521 - 530
PubMed Reference 25730668
Abstract 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 ß-peptide (Aß) precursor protein leads to early cerebral microvascular
degeneration, blood flow reductions and dysregulation and BBB breakdown, and to
accelerated amyloid ß-peptide (Aß) pathology, reduced Aß 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.

Investigators with authorship
E. Dale AbelUniversity of Iowa