title: Active Aβ vaccination fails to enhance amyloid clearance in a mouse model of Alzheimer's disease with Aβ42-driven pathology.
abstract: Aβ vaccination has been shown to induce remarkable clearance of brain amyloid plaques in mouse models of Alzheimer's disease (AD). However, the extent to which antibody-mediated Aβ clearance is affected by predominant formation of Aβ42 over Aβ40 is unclear. Here we demonstrate for the first time that in a mouse model carrying the human APP mutations KM670/671NL and the human PS1 mutation P166L, Aβ vaccination does not result in plaque clearance. This was in spite of the strong T- and B-cell immune responses evoked under the DR1501 genetic background and the activation of microglia at sites of Aβ plaques. Our findings suggest the existence of antibody-resistant forms of Aβ deposits in the brain consisting of primarily Aβ42, and shed light on the mechanisms of antibody-dependent amyloid clearance as well as novel therapeutic strategies for AD.
authors.affiliation: The Shraga Segal Department of Microbiology and Immunology, Faculty of Health Sciences, and The National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev,Beer-Sheva, Israel.
authors.forename: Anna
authors.initials: A
authors.lastname: Nemirovsky
authors.forename: Jenny
authors.initials: J
authors.lastname: Shapiro
authors.forename: Rona
authors.initials: R
authors.lastname: Baron
authors.forename: Alex
authors.initials: A
authors.lastname: Kompaniets
authors.forename: Alon
authors.initials: A
authors.lastname: Monsonego
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000276:immunology* / Q000628:therapy*; D000682:Amyloid / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000276:immunology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005620:Freund's Adjuvant / Q000276:immunology; D006801:Humans; D016233:Immunotherapy, Active / Q000379:methods*; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D009154:Mutation / Q000235:genetics; D010446:Peptide Fragments / Q000276:immunology*; D053764:Presenilin-1 / Q000235:genetics; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; C508853:PSEN1 protein, human; D010446:Peptide Fragments; D053764:Presenilin-1; C075222:amyloid beta-protein (1-42); D005620:Freund's Adjuvant