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

被引：320

作者：

Baruch, Kuti ^{[1
]}

Deczkowska, Aleksandra ^{[1
]}

Rosenzweig, Neta ^{[1
]}

Tsitsou-Kampeli, Afroditi ^{[1
]}

Sharif, Alaa Mohammad ^{[1
]}

Matcovitch-Natan, Orit ^{[1
,2
]}

Kertser, Alexander ^{[1
]}

David, Eyal ^{[2
]}

Amit, Ido ^{[2
]}

Schwartz, Michal ^{[1
]}

机构：

[1] Weizmann Inst Sci, Dept Neurobiol, IL-76100 Rehovot, Israel

[2] Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel

来源：

NATURE MEDICINE | 2016年 / 22卷 / 02期

基金：

欧洲研究理事会;

关键词：

CHOROID-PLEXUS; NEURODEGENERATION; RECRUITMENT; MACROPHAGES; ACTIVATION;

D O I：

10.1038/nm.4022

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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)-gamma-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-beta (A beta) 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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收藏

页码：135 / 137

页数：3

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