P1‐351: A novel approach to diagnosis: Antigen‐antibody disassociation in Alzheimer's disease

With the ever-increasing population of aged individuals who are at risk of developing Alzheimer disease (AD) there is an urgent need for a sensitive, specific and preferably, non-invasive, diagnostic standard. The majority of efforts to date have focused on auto-antibodies against amyloid protein, not only as a potential treatment, but as a reliable biomarker of AD pathology. Naturally occurring antibodies against amyloid are found in the CSF and plasma of patients with AD as well as in healthy control subjects. However, some of the antibody is undoubtedly present in antigen-antibody complexes. Thus, accurately measuring total amounts of antigen or antibody requires unmasking, or dissociation of the antigen-antibody complexes, as has been shown in animal studies. Here, we describe a simple assay using human plasma samples whereby, using a reliable and reproducible technique for dissociating antibody-antigen complexes, we found significant differences in serum antibodies to amyloid-beta between AD and aged-matched control subjects. In contrast to evaluating antibody levels from non-dissociated serum samples, which in both our hands and in published reports show new identical levels between AD and control samples, using dissociated serum samples, antibodies directed against amyloid-beta always resulted in the AD and control populations demonstrating significant differences. While the current study demonstrates the relevance of measuring total antibody, bound and unbound, against amyloid-beta in AD, this technique may be applicable to other diseases such as AIDS and hepatitis B where determination of antigen and antibody levels are important tools for disease diagnosis and assessing disease progression.