Decreased glucose transporters correlate to abnormal hyperphosphorylation of tau in Alzheimer disease.
Brain glucose uptake/metabolism is impaired in Alzheimer disease (AD). Here, we report that levels of the two major brain glucose transporters (GLUT1 and GLUT3) responsible for glucose uptake into neurons were decreased in AD brain. This decrease correlated to the decrease in O-GlcNAcylation, to the hyperphosphorylation of tau, and to the density of neurofibrillary tangles in human brains. We also found down-regulation of hypoxia-inducible factor 1, a major regulator of GLUT1 and GLUT3, in AD brain. These studies provide a possible mechanism by which GLUT1 and GLUT3 deficiency could cause impaired brain glucose uptake/metabolism and contribute to neurodegeneration via down-regulation of O-GlcNAcylation and hyperphosphorylation of tau in AD.
Liu
Ying
Y
Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314, USA.
Liu
Fei
F
Iqbal
Khalid
K
Grundke-Iqbal
Inge
I
Gong
Cheng-Xin
CX
D000215:Acylation; D000544:Alzheimer Disease / Q000378:metabolism*; D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D051272:Glucose Transporter Type 1 / Q000378:metabolism*; D051273:Glucose Transporter Type 2 / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation; D016875:tau Proteins / Q000378:metabolism*
D051272:Glucose Transporter Type 1; D051273:Glucose Transporter Type 2; D016875:tau Proteins