Pd-1 immune checkpoint blockade reduces pathology and improves memory in mouse models of alzheimer's disease

ABSTRACT Systemic immune suppression may curtail the ability to mount the protective, cell-mediated immune responses that are needed for brain repair. By using mouse models of

Alzheimer's disease (AD), we show that immune checkpoint blockade directed against the programmed death-1 (PD-1) pathway evokes an interferon (IFN)-γ–dependent systemic immune response,

which is followed by the recruitment of monocyte-derived macrophages to the brain. When induced in mice with established pathology, this immunological response leads to clearance of

cerebral amyloid-β (Aβ) plaques and improved cognitive performance. Repeated treatment sessions were required to maintain a long-lasting beneficial effect on disease pathology. These

findings suggest that immune checkpoints may be targeted therapeutically in AD. Access through your institution Buy or subscribe This is a preview of subscription content, access via your

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* Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS TARGETING INNATE IMMUNITY TO PROTECT AND CURE ALZHEIMER’S DISEASE:

OPPORTUNITIES AND PITFALLS Article 14 April 2021 NEUROINFLAMMATION IN ALZHEIMER DISEASE Article 09 December 2024 A MULTI-TARGETING IMMUNOTHERAPY AMELIORATES MULTIPLE FACETS OF ALZHEIMER’S

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Article  CAS  Google Scholar  Download references ACKNOWLEDGEMENTS We thank I. Slutsky (Tel Aviv University, Tel Aviv, Israel) for APP/PS1 mice, S. Schwarzbaum for proofreading the

manuscript, M. Azulai for animal handling and the Krenter Institute for equipment grant support. This work was supported by Advanced European Research Council (ERC) grants (no. 232835 to

M.S. and no. 309788 to I.A.), by the EU Seventh Framework Program HEALTH-2011 (grant no. 279017 to M.S.), by an Israeli Science Foundation grant (no. 1782/11 to I.A.) and by the

Weizmann-Tanz collaboration for research in Alzheimer's disease (to M.S.). M.S. holds the Maurice and Ilse Katz Professorial Chair in Neuroimmunology. AUTHOR INFORMATION AUTHORS AND

AFFILIATIONS * Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel Kuti Baruch, Aleksandra Deczkowska, Neta Rosenzweig, Afroditi Tsitsou-Kampeli, Alaa Mohammad Sharif,

 Orit Matcovitch-Natan, Alexander Kertser & Michal Schwartz * Department of Immunology, Weizmann Institute of Science, Rehovot, Israel Orit Matcovitch-Natan, Eyal David & Ido Amit

Authors * Kuti Baruch View author publications You can also search for this author inPubMed Google Scholar * Aleksandra Deczkowska View author publications You can also search for this

author inPubMed Google Scholar * Neta Rosenzweig View author publications You can also search for this author inPubMed Google Scholar * Afroditi Tsitsou-Kampeli View author publications You

can also search for this author inPubMed Google Scholar * Alaa Mohammad Sharif View author publications You can also search for this author inPubMed Google Scholar * Orit Matcovitch-Natan

View author publications You can also search for this author inPubMed Google Scholar * Alexander Kertser View author publications You can also search for this author inPubMed Google Scholar

* Eyal David View author publications You can also search for this author inPubMed Google Scholar * Ido Amit View author publications You can also search for this author inPubMed Google

Scholar * Michal Schwartz View author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS K.B. and M.S. conceived and designed the study. K.B., A.D., N.R.,

A.T.-K., A.M.S. and A.K. performed experiments and analyzed and interpreted the data. O.M.-N. and E.D., under the supervision of I.A., performed RNA-seq analysis. K.B. and A.D. prepared the

data for presentation. The manuscript was written by K.B. and M.S. CORRESPONDING AUTHORS Correspondence to Kuti Baruch or Michal Schwartz. ETHICS DECLARATIONS COMPETING INTERESTS K.B. and

M.S. are inventors of intellectual property related to this work. This study was partly funded by ImmunoBrain Checkpoint Ltd. SUPPLEMENTARY INFORMATION SUPPLEMENTARY TEXT AND FIGURES

Supplementary Figures 1–2 and Supplementary Table Legends (PDF 468 kb) SUPPLEMENTARY TABLE 1 Choroid plexus response to PD-1 blockade in 5XFAD mice (XLSX 1117 kb) SUPPLEMENTARY TABLE 2 Gene

ontology analysis of choroid plexus response to PD-1 blockade in 5XFAD mice (XLSX 9 kb) SUPPLEMENTARY TABLE 3 RNA-seq analysis of myeloid cells sorted from the brains of 5XFAD mice following

PD-1 blockade (XLSX 1088 kb) RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Baruch, K., Deczkowska, A., Rosenzweig, N. _et al._ PD-1 immune checkpoint

blockade reduces pathology and improves memory in mouse models of Alzheimer's disease. _Nat Med_ 22, 135–137 (2016). https://doi.org/10.1038/nm.4022 Download citation * Received: 12

October 2015 * Accepted: 04 December 2015 * Published: 18 January 2016 * Issue Date: February 2016 * DOI: https://doi.org/10.1038/nm.4022 SHARE THIS ARTICLE Anyone you share the following

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