PD-1 Immune Checkpoint Blockade Reduces Pathology and Improves Memory in Mouse Models of Alzheimer's Disease

Overview

Journal Nat Med

Specialties General Medicine
Molecular Biology

Date 2016 Jan 19

PMID 26779813

Citations 200

Authors

Kuti Baruch

Aleksandra Deczkowska

Neta Rosenzweig

Afroditi Tsitsou-Kampeli

Alaa Mohammad Sharif

Orit Matcovitch-Natan

Alexander Kertser

Eyal David

Ido Amit

Michal Schwartz

Affiliations

Soon will be listed here.

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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