Visualization of reactive astrocytes in living brain of Alzheimer's disease patient

Nam, M.-H.; Ko, H. Y.; Lee, S.; Park, Y. M.; Hyeon, S. J.; Won, W.; Kim, S. Y.; Jo, H. H.; Chung, J.-I.; Han, Y.-E.; Lee, G.-H.; Ju, Y.; Stein, T. D.; Kong, M.; Lee, H.; Lee, S. E.; Oh, S.-J.; Chun, J.-H.; Park, K. D.; Ryu, H.; Yun, M.; Lee, C. J. J.

doi:10.1101/2021.04.13.439744

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bioRxiv · 10.1101/2021.04.13.439744

Visualization of reactive astrocytes in living brain of Alzheimer's disease patient

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Abstract

An early appearance of reactive astrocytes is a hallmark of Alzheimers disease (AD)1,2, providing a substrate for early diagnostic neuroimaging targets. However, there is no clinically validated neuroimaging probe to visualize the reactive astrogliosis in the human brain in vivo. Here, we report that PET/CT imaging with 11C-acetate and 18F-fluorodeoxyglucose (18F-FDG) functionally visualizes the reactive astrocyte-mediated neuronal hypometabolism in the brains with neuroinflammation and AD. We demonstrate that reactive astrocytes excessively absorb acetate through elevated monocarboxylate transporter-1 (MCT1), leading to aberrant GABA synthesis and release which suppresses neuronal glucose uptake through decreased glucose transporter-3 (GLUT3) in both animal and human brains. We propose the non-invasive functional PET/CT imaging for astrocytic acetate-hypermetabolism and neuronal glucose-hypometabolism as an advanced diagnostic strategy for early stages of AD.

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Nam, M.-H., Ko, H. Y., Lee, S., Park, Y. M., Hyeon, S. J., Won, W., Kim, S. Y., Jo, H. H., Chung, J.-I., Han, Y.-E., Lee, G.-H., Ju, Y., Stein, T. D., Kong, M., Lee, H., Lee, S. E., Oh, S.-J., Chun, J.-H., Park, K. D., Ryu, H., Yun, M., Lee, C. J. J.. 2021-04-14. Visualization of reactive astrocytes in living brain of Alzheimer's disease patient. https://doi.org/10.1101/2021.04.13.439744

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