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dc.contributor.authorKim, Ki
dc.contributor.authorWang, Xin
dc.contributor.authorRagonnaud, Emeline
dc.contributor.authorBodogai, Monica
dc.contributor.authorIllouz, Tomer
dc.contributor.authorDeLuca, Marisa
dc.contributor.authorMcDevitt, Ross A.
dc.contributor.authorGusev, Fedor
dc.contributor.authorOkun, Eitan
dc.contributor.authorRogaev, Evgeny I.
dc.contributor.authorBiragyn, Arya
dc.date2022-08-11T08:10:00.000
dc.date.accessioned2022-08-23T16:51:36Z
dc.date.available2022-08-23T16:51:36Z
dc.date.issued2021-04-12
dc.date.submitted2021-08-10
dc.identifier.citation<p>Kim K, Wang X, Ragonnaud E, Bodogai M, Illouz T, DeLuca M, McDevitt RA, Gusev F, Okun E, Rogaev E, Biragyn A. Therapeutic B-cell depletion reverses progression of Alzheimer's disease. Nat Commun. 2021 Apr 12;12(1):2185. doi: 10.1038/s41467-021-22479-4. PMID: 33846335; PMCID: PMC8042032. <a href="https://doi.org/10.1038/s41467-021-22479-4">Link to article on publisher's site</a></p>
dc.identifier.issn2041-1723 (Linking)
dc.identifier.doi10.1038/s41467-021-22479-4
dc.identifier.pmid33846335
dc.identifier.urihttp://hdl.handle.net/20.500.14038/41890
dc.description.abstractThe function of B cells in Alzheimer's disease (AD) is not fully understood. While immunoglobulins that target amyloid beta (Abeta) may interfere with plaque formation and hence progression of the disease, B cells may contribute beyond merely producing immunoglobulins. Here we show that AD is associated with accumulation of activated B cells in circulation, and with infiltration of B cells into the brain parenchyma, resulting in immunoglobulin deposits around Abeta plaques. Using three different murine transgenic models, we provide counterintuitive evidence that the AD progression requires B cells. Despite expression of the AD-fostering transgenes, the loss of B cells alone is sufficient to reduce Abeta plaque burden and disease-associated microglia. It reverses behavioral and memory deficits and restores TGFbeta(+) microglia, respectively. Moreover, therapeutic depletion of B cells at the onset of the disease retards AD progression in mice, suggesting that targeting B cells may also benefit AD patients.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=33846335&dopt=Abstract">Link to Article in PubMed</a></p>
dc.rightsCopyright © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectB cells
dc.subjectNeuroimmunology
dc.subjectTranslational immunology
dc.subjectAlzheimer's disease
dc.subjectImmunology and Infectious Disease
dc.subjectNervous System Diseases
dc.subjectNeurology
dc.subjectNeuroscience and Neurobiology
dc.subjectPsychiatry and Psychology
dc.subjectTranslational Medical Research
dc.titleTherapeutic B-cell depletion reverses progression of Alzheimer's disease
dc.typeJournal Article
dc.source.journaltitleNature communications
dc.source.volume12
dc.source.issue1
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=5731&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/4698
dc.identifier.contextkey24268462
refterms.dateFOA2022-08-23T16:51:36Z
html.description.abstract<p>The function of B cells in Alzheimer's disease (AD) is not fully understood. While immunoglobulins that target amyloid beta (Abeta) may interfere with plaque formation and hence progression of the disease, B cells may contribute beyond merely producing immunoglobulins. Here we show that AD is associated with accumulation of activated B cells in circulation, and with infiltration of B cells into the brain parenchyma, resulting in immunoglobulin deposits around Abeta plaques. Using three different murine transgenic models, we provide counterintuitive evidence that the AD progression requires B cells. Despite expression of the AD-fostering transgenes, the loss of B cells alone is sufficient to reduce Abeta plaque burden and disease-associated microglia. It reverses behavioral and memory deficits and restores TGFbeta(+) microglia, respectively. Moreover, therapeutic depletion of B cells at the onset of the disease retards AD progression in mice, suggesting that targeting B cells may also benefit AD patients.</p>
dc.identifier.submissionpathoapubs/4698
dc.contributor.departmentDepartment of Psychiatry
dc.source.pages2185


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Copyright © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Except where otherwise noted, this item's license is described as Copyright © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.