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

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; Erich Gulbins; Martin Reichel; Johannes Kornhuber; Chang Won Hong; Changho Kim; Seung Hyun Kim; Edward H. Schuchman; Hee Kyung Jin; Jae sung Bae

doi:10.1038/s41467-023-37316-z

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

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, Erich Gulbins, Martin Reichel, Johannes Kornhuber, Chang Won Hong, Changho Kim, Seung Hyun Kim, Edward H. SchuchmanHee Kyung Jin, Jae sung Bae

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

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.

Original language	English
Article number	1631
Journal	Nature Communications
Volume	14
Issue number	1
DOIs	https://doi.org/10.1038/s41467-023-37316-z
State	Published - Dec 2023

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Choi, B. J., Park, M. H., Park, K. H., Han, W. H., Yoon, H. J., Jung, H. Y., Hong, J. Y., Chowdhury, M. R., Kim, K. Y., Lee, J., Song, I. S., Pang, M., Choi, M. K., Gulbins, E., Reichel, M., Kornhuber, J., Hong, C. W., Kim, C., Kim, S. H., ... Bae, J. S. (2023). Immunotherapy targeting plasma ASM is protective in a mouse model of Alzheimer’s disease. Nature Communications, 14(1), Article 1631. https://doi.org/10.1038/s41467-023-37316-z

@article{15f78afd230b449c8602b62ac4dbbf7b,

title = "Immunotherapy targeting plasma ASM is protective in a mouse model of Alzheimer{\textquoteright}s disease",

abstract = "Acid sphingomyelinase (ASM) has been implicated in neurodegenerative disease pathology, including Alzheimer{\textquoteright}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.",

author = "Choi, {Byung Jo} and Park, {Min Hee} and Park, {Kang Ho} and Han, {Wan Hui} and Yoon, {Hee Ji} and Jung, {Hye Yoon} and Hong, {Ju Yeon} and Chowdhury, {Md Riad} and Kim, {Kyung Yeol} and Jihoon Lee and Song, {Im Sook} and Minyeong Pang and Choi, {Min Koo} and Erich Gulbins and Martin Reichel and Johannes Kornhuber and Hong, {Chang Won} and Changho Kim and Kim, {Seung Hyun} and Schuchman, {Edward H.} and Jin, {Hee Kyung} and Bae, {Jae sung}",

note = "Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

month = dec,

doi = "10.1038/s41467-023-37316-z",

language = "English",

volume = "14",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

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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, 'Immunotherapy targeting plasma ASM is protective in a mouse model of Alzheimer’s disease', Nature Communications, vol. 14, no. 1, 1631. https://doi.org/10.1038/s41467-023-37316-z

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AU - Choi, Byung Jo

AU - Park, Min Hee

AU - Park, Kang Ho

AU - Han, Wan Hui

AU - Yoon, Hee Ji

AU - Jung, Hye Yoon

AU - Hong, Ju Yeon

AU - Chowdhury, Md Riad

AU - Kim, Kyung Yeol

AU - Lee, Jihoon

AU - Song, Im Sook

AU - Pang, Minyeong

AU - Choi, Min Koo

AU - Gulbins, Erich

AU - Reichel, Martin

AU - Kornhuber, Johannes

AU - Hong, Chang Won

AU - Kim, Changho

AU - Kim, Seung Hyun

AU - Schuchman, Edward H.

AU - Jin, Hee Kyung

AU - Bae, Jae sung

PY - 2023/12

Y1 - 2023/12

N2 - 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.

AB - 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.

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SN - 2041-1723

VL - 14

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 1631

ER -

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

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