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Immunotherapy targeting plasma ASM is protective in a mouse model of Alzheimer’s disease

Author

Listed:
  • Byung Jo Choi

    (Kyungpook National University
    Kyungpook National University)

  • Min Hee Park

    (Kyungpook National University
    Kyungpook National University)

  • Kang Ho Park

    (Kyungpook National University
    Kyungpook National University)

  • Wan Hui Han

    (Kyungpook National University
    Kyungpook National University)

  • Hee Ji Yoon

    (Kyungpook National University
    Kyungpook National University)

  • Hye Yoon Jung

    (Kyungpook National University
    Kyungpook National University)

  • Ju Yeon Hong

    (Kyungpook National University
    Kyungpook National University)

  • Md Riad Chowdhury

    (Kyungpook National University
    Kyungpook National University)

  • Kyung Yeol Kim

    (Kyungpook National University
    Kyungpook National University)

  • Jihoon Lee

    (Kyungpook National University)

  • Im-Sook Song

    (Kyungpook National University)

  • Minyeong Pang

    (Dankook University)

  • Min-Koo Choi

    (Dankook University)

  • Erich Gulbins

    (University of Duisburg-Essen)

  • Martin Reichel

    (Friedrich-Alexander-University of Erlangen-Nuremberg)

  • Johannes Kornhuber

    (Friedrich-Alexander-University of Erlangen-Nuremberg)

  • Chang-Won Hong

    (Kyungpook National University)

  • Changho Kim

    (Kyungpook National University)

  • Seung Hyun Kim

    (Hanyang University College of Medicine)

  • Edward H. Schuchman

    (Icahn School of Medicine at Mount Sinai)

  • Hee Kyung Jin

    (Kyungpook National University
    Kyungpook National University)

  • Jae-sung Bae

    (Kyungpook National University
    Kyungpook National University)

Abstract

Acid sphingomyelinase (ASM) has been implicated in neurodegenerative disease pathology, including Alzheimer’s disease (AD). However, the specific role of plasma ASM in promoting these pathologies is poorly understood. Herein, we explore plasma ASM as a circulating factor that accelerates neuropathological features in AD by exposing young APP/PS1 mice to the blood of mice overexpressing ASM, through parabiotic surgery. Elevated plasma ASM was found to enhance several neuropathological features in the young APP/PS1 mice by mediating the differentiation of blood-derived, pathogenic Th17 cells. Antibody-based immunotherapy targeting plasma ASM showed efficient inhibition of ASM activity in the blood of APP/PS1 mice and, interestingly, led to prophylactic effects on neuropathological features by suppressing pathogenic Th17 cells. Our data reveals insights into the potential pathogenic mechanisms underlying AD and highlights ASM-targeting immunotherapy as a potential strategy for further investigation.

Suggested Citation

  • Byung Jo Choi & Min Hee Park & Kang Ho Park & Wan Hui Han & Hee Ji Yoon & Hye Yoon Jung & Ju Yeon Hong & Md Riad Chowdhury & Kyung Yeol Kim & Jihoon Lee & Im-Sook Song & Minyeong Pang & Min-Koo Choi &, 2023. "Immunotherapy targeting plasma ASM is protective in a mouse model of Alzheimer’s disease," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37316-z
    DOI: 10.1038/s41467-023-37316-z
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    References listed on IDEAS

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