Decreased glucose transporters correlate to abnormal hyperphosphorylation of tau in Alzheimer disease

• Published in: FEBS letters 2008-01, Vol.582 (2), p.359-364
• Main Authors: Liu, Ying, Liu, Fei, Iqbal, Khalid, Grundke-Iqbal, Inge, Gong, Cheng-Xin
• Format: Article
• Language: English
• Subjects: Acylation; Alzheimer disease; Alzheimer Disease - metabolism; Astrocytes - metabolism; Brain - metabolism; GFAP; GlcNAc; glial fibrillary acidic protein; Glucose Transporter Type 1 - metabolism; Glucose Transporter Type 2 - metabolism; Glucose transporters; GLUTs; HIF-1; Humans; Hyperphosphorylation; Hypoxia-inducible factor; hypoxia-inducible factor 1; neurofibrillary tangles; NFTs; O-GlcNAcylation; Phosphorylation; Tau; tau Proteins - metabolism; β-N-acetylglucosamine
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2007.12.035

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.