title: Increased Number of Plasma B Cells Producing Autoantibodies Against Aβ42 Protofibrils in Alzheimer's Disease.
abstract: The Alzheimer's disease (AD)-related peptide amyloid-β (Aβ) has a propensity to aggregate into various assemblies including toxic soluble Aβ protofibrils. Several studies have reported the existence of anti-Aβ antibodies in humans. However, it is still debated whether levels of anti-Aβ antibodies are altered in AD patients compared to healthy individuals. Formation of immune complexes with plasma Aβ makes it difficult to reliably measure the concentration of circulating anti-Aβ antibodies with certain immunoassays, potentially leading to an underestimation. Here we have investigated anti-Aβ antibody production on a cellular level by measuring the amount of anti-Aβ antibody producing cells instead of the plasma level of anti-Aβ antibodies. To our knowledge, this is the first time the anti-Aβ antibody response in plasma has been compared in AD patients and age-matched healthy individuals using the enzyme-linked immunospot (ELISpot) technique. Both AD patients and healthy individuals had low levels of B cells producing antibodies binding Aβ40 monomers, whereas the number of cells producing antibodies toward Aβ42 protofibrils was higher overall and significantly higher in AD compared to healthy controls. This study shows, by an alternative and reliable method, that there is a specific immune response to the toxic Aβ protofibrils, which is significantly increased in AD patients.
authors.affiliation: Department of Public Health & Caring Sciences/Molecular Geriatrics, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Sofia
authors.initials: S
authors.lastname: Söllvander
authors.affiliation: Department of Public Health & Caring Sciences/Molecular Geriatrics, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Frida
authors.initials: F
authors.lastname: Ekholm-Pettersson
authors.affiliation: Department of Public Health & Caring Sciences/Molecular Geriatrics, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Rose-Marie
authors.initials: RM
authors.lastname: Brundin
authors.affiliation: Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Westman
authors.affiliation: Department of Public Health & Caring Sciences/Molecular Geriatrics, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Lena
authors.initials: L
authors.lastname: Kilander
authors.affiliation: Mabtech AB, Nacka Strand, Sweden.
authors.forename: Staffan
authors.initials: S
authors.lastname: Paulie
authors.affiliation: Department of Public Health & Caring Sciences/Molecular Geriatrics, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Lannfelt
authors.affiliation: Department of Public Health & Caring Sciences/Molecular Geriatrics, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Dag
authors.initials: D
authors.lastname: Sehlin
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000276:immunology*; D016229:Amyloid beta-Peptides / Q000276:immunology* / Q000378:metabolism; D001323:Autoantibodies / Q000378:metabolism*; D001402:B-Lymphocytes / Q000378:metabolism*; D019921:Biotinylation; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008609:Mental Status Schedule; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D001323:Autoantibodies; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)
keywords: Amyloid-β; amyloid-β protofibrils; anti-amyloid-β antibodies; enzyme-linked immunospot assay