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A Key Mediator and Imaging Target in Alzheimer’s Disease: Unlocking the Role of Reactive Astrogliosis Through MAOB

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Abstract

Astrocytes primarily maintain physiological brain homeostasis. However, under various pathological conditions, they can undergo morphological, transcriptomic, and functional transformations, collectively referred to as reactive astrogliosis. Recent studies have accumulated lines of evidence that reactive astrogliosis plays a crucial role in the pathology of Alzheimer’s disease (AD). In particular, monoamine oxidase B, a mitochondrial enzyme mainly expressed in astrocytes, significantly contributes to neuronal dysfunction and neurodegeneration in AD brains. Moreover, it has been reported that reactive astrogliosis precedes other pathological hallmarks such as amyloid-beta plaque deposition and tau tangle formation in AD. Due to the early onset and profound impact of reactive astrocytes on pathology, there have been extensive efforts in the past decade to visualize these cells in the brains of AD patients using positron emission tomography (PET) imaging. In this review, we summarize the recent studies regarding the essential pathological importance of reactive astrocytes in AD and their application as a target for PET imaging.

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Acknowledgements

In this paper, we used figures from the previously published papers to help readers understand. Fig. 1a was published in "Tracking pathophysiological orocesses in Alzheimer's disease: an updated hypothetical model of dynamic biomakers" Lancet Neurol 2013;12:207-16 and reprint permission was obtained from Elsevier. Fig. 1b was published in "Alzheimer Disease: An Update on Pathobiology and Treatmant Strategies" Cell 2019;179(2):312-339 and reprint permission was abtained from Elsevier. Fig. 1c was published "Astrocyte Biomakers in Alzheimer's Disease" Trends Mol Med 2019;25(2):77-95 and reprint permission was obtained from Elsevier. Fig. 1d was published in "Reactive astroliosis: A friend or foe in the pathogenesis of Alzheimer's disease" J Neurochem 2023;164(3):309-24 and wa licensed under the Creative commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction."

Funding

This study was supported by IBS-R001-D2 from the Institute for Basic Science funded by the Ministry of Science and ICT to C.J.L.; NRF-2018M3C7A1056898 and NRF-2020R1A2B5B01098109 from National Research Foundation (NRF) of Korea to M.Y.; 2022R1C1C1006167 and NRF-2018M3C7A1056897 from NRF to M.-H.N.

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Authors and Affiliations

  1. Brain Science Institute, Korea Institute of Science and Technology, Seoul, Republic of Korea

    Min-Ho Nam & Heesu Na

  2. Center for Cognition and Sociality, Institute for Basic Science, Daejeon, Republic of Korea

    C. Justin Lee

  3. Department of Nuclear Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea

    Mijin Yun

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  1. Min-Ho Nam
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Contributions

The study was designed by MY. First draft was written by M-HN, HN, and MY. Revision and editing of the manuscript were conducted by M-HN, CJL, and MY. All authors have read and approved the final manuscript.

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Correspondence to Min-Ho Nam, C. Justin Lee or Mijin Yun.

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Min-Ho Nam, Heesu Na, C. Justin Lee, and Mijin Yun declare no conflict of interest.

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Nam, MH., Na, H., Justin Lee, C. et al. A Key Mediator and Imaging Target in Alzheimer’s Disease: Unlocking the Role of Reactive Astrogliosis Through MAOB. Nucl Med Mol Imaging (2024). https://doi.org/10.1007/s13139-023-00837-y

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