Increased Levels of Antigen-Bound β-Amyloid Autoantibodies in Serum and Cerebrospinal Fluid of Alzheimer’s Disease Patients

• Published in: PloS one Vol. 8; no. 7; p. e68996
• Main Authors: Maftei, Madalina, Thurm, Franka, Schnack, Cathrin, Tumani, Hayrettin, Otto, Markus, Elbert, Thomas, Kolassa, Iris-Tatjana, Przybylski, Michael, Manea, Marilena, von Arnim, Christine A. F.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 18.07.2013; Public Library of Science (PLoS)
• Subjects: Aged; Alzheimer Disease - immunology; Alzheimer's disease; Amyloid beta-Peptides - immunology; Analytical chemistry; Antibody Specificity; Antigen-antibody complexes; Antigens; Apolipoproteins; Autoantibodies; Autoantibodies - blood; Autoantibodies - cerebrospinal fluid; Biology; Biomarkers; Biopolymers; Cerebrospinal fluid; Chemistry; Clinical trials; Cognition - physiology; Cognitive ability; Dementia; Enzyme-linked immunosorbent assay; Enzyme-Linked Immunosorbent Assay - methods; Epitopes - genetics; Female; Humans; Immune clearance; Immune response; Immune system; Immunization; Immunoglobulin G; Immunoglobulin G - blood; Immunoglobulin G - cerebrospinal fluid; Immunoglobulins; Immunotherapy; In vivo methods and tests; Laboratories; Male; Medicine; Middle Aged; Models, Statistical; Neurodegenerative diseases; Neurology; Patients; Peptides; Plasma; Proteins; Rodents; β-Amyloid; Germany
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0068996

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.