Measurement of anti-beta amyloid antibodies in human blood

The human IgG repertoire contains endogenous antibodies against beta amyloid (Aβ) that may be relevant to the pathogenesis and treatment of Alzheimer's disease. There have been widely disparate estimates of the levels of these antibodies in human plasma. We identify factors that have contributed to these disparities and describe improved methods for measuring anti-Aβ antibodies in blood. These methods include isolating immunoglobulin by thiophilic chromatography and using chaotropic salts to dislodge weakly bound antibodies without significantly reducing the binding of specific anti-Aβ antibodies. Using these methods, we show that human blood contains polyvalent IgG antibodies that bind to Aβ with relatively low avidity and specificity, as well as IgG antibodies that bind to linear and conformational epitopes on amyloid monomers and aggregates with moderate to high avidity.