title: PD-1 immune checkpoint blockade reduces pathology and improves memory in mouse models of Alzheimer's disease.
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.
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Kuti
authors.initials: K
authors.lastname: Baruch
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Deczkowska
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Neta
authors.initials: N
authors.lastname: Rosenzweig
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Afroditi
authors.initials: A
authors.lastname: Tsitsou-Kampeli
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Alaa Mohammad
authors.initials: AM
authors.lastname: Sharif
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.|Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Orit
authors.initials: O
authors.lastname: Matcovitch-Natan
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kertser
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Eyal
authors.initials: E
authors.lastname: David
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Ido
authors.initials: I
authors.lastname: Amit
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Schwartz
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000187:drug effects / Q000276:immunology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D003071:Cognition / Q000187:drug effects; D004195:Disease Models, Animal; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000187:drug effects / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D051379:Mice; D008822:Mice, Transgenic; D058225:Plaque, Amyloid / Q000276:immunology* / Q000473:pathology; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors / Q000276:immunology*; D017423:Sequence Analysis, RNA; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C545487:APP protein, human; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D000906:Antibodies; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor; D007371:Interferon-gamma