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Little is known about the mechanism causing GLUT1 dysregulation in AD. GLUT1 expression is controlled by hypoxia-inducible factor 1 (HIF1,). Given that HIF1 is down-regulated in AD15, it is conceivable that HIF1 suppression leads to reduced GLUT1 expression. However, earlier studies have indicated that SLC2A1 mRNA is not reduced in AD, implicating post-translational mechanisms8.
Thus, further studies on the molecular bases of GLUT1 reduction are needed to provide some indication of how to counteract it.
Irrespective of the many questions outstanding, the data of Winkler et al.4 demonstrate a multifaceted role of glucose transport in the maintenance of brain structure and function, and unveil a damaging interaction with AD pathology. This may open new therapeutic avenues for this devastating neurodegenerative disease.
COMPETING FINANCIAL INTERESTS
The author declares no competing financial interests.
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Endothelial GLUT1 deficiency
Cognitive deficits
Glucose
LRP1
Reduced brain glucose uptake
Reduced A clearance
A
BBB leakage
Hypoperfusion
Synaptic dysfunction and neurodegeneration
Altered homeostasis Amyloid pathology
Energy deficit
Microvascular rarefaction
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