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Sugar and Alzheimer's disease: a bittersweet truth

Nature Neuroscience volume 18, pages 477–478 (2015)Cite this article

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Reductions in brain glucose metabolism have long been associated with Alzheimer's disease. A study now demonstrates that the endothelial glucose transporter GLUT1 is vital for maintaining brain energy metabolism and vascular clearance of amyloid-β.

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 function1. The job of delivering such a large amount of glucose across the blood-brain barrier (BBB) falls exclusively to endothelial cells lining cerebral blood vessels. Endothelial cells make up less than 1% of brain cells, but are loaded with GLUT1, a specialized transporter protein that helps glucose cross the BBB and enter the brain2. Defects in cerebral glucose metabolism in Alzheimer's disease (AD), the most frequent cause of dementia, have suggested that 'brain starvation' could be involved in the disease process3. However, proof that this mechanism, albeit plausible, could induce brain dysfunction and contribute to AD has been lacking. As reported in this issue of Nature Neuroscience, Winkler et al.4 used mouse models to demonstrate that GLUT1 deficiency leads to profound changes in vascular, BBB and neuronal function that are particularly damaging in the setting of AD pathology. In addition to highlighting a new function of GLUT1 in vascular homeostasis, these findings establish endothelial GLUT1 as critical factor in maintaining brain health and a potential therapeutic target in AD.

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Figure 1: Mechanisms of brain dysfunction and damage caused by GLUT1 deficiency.

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  1. Costantino Iadecola is at the Fail Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, New York, USA.,

    Costantino Iadecola

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Iadecola, C. Sugar and Alzheimer's disease: a bittersweet truth. Nat Neurosci 18, 477–478 (2015). https://doi.org/10.1038/nn.3986

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