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

Kuti Baruch; Aleksandra Deczkowska; Neta Rosenzweig; Afroditi Tsitsou-Kampeli; Alaa Mohammad Sharif; Orit Matcovitch-Natan; Alexander Kertser; Eyal David; Ido Amit; Michal Schwartz

doi:10.1038/nm.4022

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

Kuti Baruch, Aleksandra Deczkowska, Neta Rosenzweig, Afroditi Tsitsou-Kampeli, Alaa Mohammad Sharif, Orit Matcovitch-Natan, Alexander Kertser, Eyal David, Ido Amit, Michal Schwartz

Weizmann Institute of Science

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

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.

Original language	English
Pages (from-to)	135-137
Number of pages	3
Journal	Nature Medicine
Volume	22
Issue number	2
DOIs	https://doi.org/10.1038/nm.4022
State	Published - 1 Feb 2016

All Science Journal Classification (ASJC) codes

General Biochemistry,Genetics and Molecular Biology

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10.1038/nm.4022

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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.",

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AU - Baruch, Kuti

AU - Deczkowska, Aleksandra

AU - Rosenzweig, Neta

AU - Tsitsou-Kampeli, Afroditi

AU - Sharif, Alaa Mohammad

AU - Matcovitch-Natan, Orit

AU - Kertser, Alexander

AU - David, Eyal

AU - Amit, Ido

AU - Schwartz, Michal

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AB - 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.

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

Abstract

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