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

Nam, Min-Ho, Ko, Hae Young, Lee, Sangwon, Park, Yongmin Mason, Hyeon, Seung Jae, Won, Woojin, Kim, Seon Yoo, Jo, Han Hee +14 more·2021
DOI 10.1101/2021.04.13.439744

Preprint — published as 10.1093/brain/awad037

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Abstract

An early appearance of reactive astrocytes is a hallmark of Alzheimer’s 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 11 C-acetate and 18 F-fluorodeoxyglucose ( 18 F-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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Cited by

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Authors
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.
ORCID
Publisher
openRxiv
Published
2021-04-14
DOI
10.1101/2021.04.13.439744
Cited by
4
References
1
Type
Preprint
Licence
creativecommons.org/licenses/by-nc-nd/4.0/ (vor)

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