PD-1 immune checkpoint blockade reduces pathology and improves memory in mouse models of Alzheimer's disease - PubMed (original) (raw)
doi: 10.1038/nm.4022. Epub 2016 Jan 18.
Affiliations
- PMID: 26779813
- DOI: 10.1038/nm.4022
PD-1 immune checkpoint blockade reduces pathology and improves memory in mouse models of Alzheimer's disease
Kuti Baruch et al. Nat Med. 2016 Feb.
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.
Comment in
- Alzheimer disease: Cancer immunotherapy drug reduces symptoms of Alzheimer disease in mice.
Malkki H. Malkki H. Nat Rev Neurol. 2016 Mar;12(3):126. doi: 10.1038/nrneurol.2016.8. Epub 2016 Jan 29. Nat Rev Neurol. 2016. PMID: 26823148 No abstract available. - Neurodegenerative disease: Immunotherapy opportunity emerges for Alzheimer disease.
Crunkhorn S. Crunkhorn S. Nat Rev Drug Discov. 2016 Mar;15(3):158. doi: 10.1038/nrd.2016.38. Epub 2016 Feb 26. Nat Rev Drug Discov. 2016. PMID: 26915450 No abstract available.
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References
- Nat Commun. 2015 Aug 18;6:7967 - PubMed
- Science. 2014 Oct 3;346(6205):89-93 - PubMed
- Trends Pharmacol Sci. 2015 Sep;36(9):587-95 - PubMed
- Science. 2014 Feb 14;343(6172):776-9 - PubMed
- Bioinformatics. 2009 May 1;25(9):1105-11 - PubMed
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