Immunotherapy targeting plasma ASM is protective in a mouse model of Alzheimer’s disease
Choi BJ, Park MH, Park KH, Han WH, Yoon HJ, Jung HY, Hong JY, Chowdhury MR, Kim KY, Lee J, Song IS, Pang M, Choi MK, Gulbins E, Reichel M, Kornhuber J, Hong CW, Kim C, Kim SH, Schuchman EH, Jin HK, Bae Js (2023)
Publication Type: Journal article
Publication year: 2023
Journal
Book Volume: 14
Article Number: 1631
Journal Issue: 1
DOI: 10.1038/s41467-023-37316-z
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.
Authors with CRIS profile
Martin Reichel
Department of Psychiatry and Psychotherapy
Johannes Kornhuber
Lehrstuhl für Psychiatrie und Psychotherapie
Involved external institutions
Kyungpook National University
Korea, Republic of (KR)
Icahn School of Medicine at Mount Sinai
United States (USA) (US)
Dankook University / 단국대학교
Korea, Republic of (KR)
Universitätsklinikum Essen
Germany (DE)
Hanyang University / 한양대학교
Korea, Republic of (KR)
Korea, Republic of (KR)
Icahn School of Medicine at Mount Sinai
United States (USA) (US)
Dankook University / 단국대학교
Korea, Republic of (KR)
Universitätsklinikum Essen
Germany (DE)
Hanyang University / 한양대학교
Korea, Republic of (KR)
How to cite
APA:
Choi, B.J., Park, M.H., Park, K.H., Han, W.H., Yoon, H.J., Jung, H.Y.,... Bae, J.s. (2023). Immunotherapy targeting plasma ASM is protective in a mouse model of Alzheimer’s disease. Nature Communications, 14(1). https://dx.doi.org/10.1038/s41467-023-37316-z
MLA:
Choi, Byung Jo, et al. "Immunotherapy targeting plasma ASM is protective in a mouse model of Alzheimer’s disease." Nature Communications 14.1 (2023).
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