title: Increased levels of antigen-bound β-amyloid autoantibodies in serum and cerebrospinal fluid of Alzheimer's disease patients.
abstract: Recent studies have suggested a protective role of physiological β-amyloid autoantibodies (Aβ-autoantibodies) in Alzheimer's disease (AD). However, the determination of both free and dissociated Aβ-autoantibodies in serum hitherto has yielded inconsistent results regarding their function and possible biomarker value. Here we report the application of a new sandwich enzyme-linked immunosorbent assay (ELISA) for the determination of antigen-bound Aβ-autoantibodies (intact Aβ-IgG immune complexes) in serum and cerebrospinal fluid (CSF) of a total number of 112 AD patients and age- and gender-matched control subjects. Both serum and CSF levels of Aβ-IgG immune complexes were found to be significantly higher in AD patients compared to control subjects. Moreover, the levels of Aβ-IgG complexes were negatively correlated with the cognitive status across the groups, increasing with declining cognitive test performance of the subjects. Our results suggest a contribution of IgG-type autoantibodies to Aβ clearance in vivo and an increased immune response in AD, which may be associated with deficient Aβ-IgG removal. These findings may contribute to elucidating the role of Aβ-autoantibodies in AD pathophysiology and their potential application in AD diagnosis.
authors.affiliation: Laboratory of Analytical Chemistry and Biopolymer Structure Analysis, Department of Chemistry, University of Konstanz, Konstanz, Germany.
authors.forename: Madalina
authors.initials: M
authors.lastname: Maftei
authors.forename: Franka
authors.initials: F
authors.lastname: Thurm
authors.forename: Cathrin
authors.initials: C
authors.lastname: Schnack
authors.forename: Hayrettin
authors.initials: H
authors.lastname: Tumani
authors.forename: Markus
authors.initials: M
authors.lastname: Otto
authors.forename: Thomas
authors.initials: T
authors.lastname: Elbert
authors.forename: Iris-Tatjana
authors.initials: IT
authors.lastname: Kolassa
authors.forename: Michael
authors.initials: M
authors.lastname: Przybylski
authors.forename: Marilena
authors.initials: M
authors.lastname: Manea
authors.forename: Christine A F
authors.initials: CA
authors.lastname: von Arnim
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000276:immunology*; D016229:Amyloid beta-Peptides / Q000276:immunology*; D000918:Antibody Specificity; D001323:Autoantibodies / Q000097:blood* / Q000134:cerebrospinal fluid*; D003071:Cognition / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods*; D000939:Epitopes / Q000235:genetics; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000134:cerebrospinal fluid; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical
chemical_list: D016229:Amyloid beta-Peptides; D001323:Autoantibodies; D000939:Epitopes; D007074:Immunoglobulin G