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

Recent studies have suggested a protective role of physiological beta-amyloid autoantibodies (A beta-autoantibodies) in Alzheimer's disease (AD). However, the determination of both free and dissociated A beta-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 A beta-autoantibodies (intact A beta-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 A beta-IgG immune complexes were found to be significantly higher in AD patients compared to control subjects. Moreover, the levels of A beta-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 A beta clearance in vivo and an increased immune response in AD, which may be associated with deficient A beta-IgG removal. These findings may contribute to elucidating the role of A beta-autoantibodies in AD pathophysiology and their potential application in AD diagnosis.