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Nat Med. 2016 Feb;22(2):135-7. doi: 10.1038/nm.4022. Epub 2016 Jan 18.

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

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Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.


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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