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.