Dissociated amyloid-beta antibody levels as a serum biomarker for the progression of Alzheimer's disease: a population-based study.

With an ever growing 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 of disease progression. Mainstream thinking suggests that early intervention is key to maximizing the opportunity for a successful treatment regimen in AD and, as such, an early and accurate means of diagnosis is essential. In this study, we applied a recently described antibody-antigen dissociation technique to samples obtained as part of a population-based analysis of the prevalence of AD. Stratified sampling and random selection strategies were combined to obtain a representative population for screening of individuals older than 55 years. Serum antibodies to amyloid-beta (Abeta)(1-42) were measured before and after antigen dissociation. The difference between the two measurements was indicated as the dissociation delta (Delta). Our analyses showed that the levels of dissociated antibody in AD patients were always significantly different from controls and that levels of Abeta antibody after dissociation, but not those of non-dissociated antibody, correlated negatively (p<0.05) with both duration of the disease and age in the AD patients. Moreover, the change in concentration of Abeta antibody from pre- to post-dissociation (i.e., the dissociation Delta) directly reflected the progression of AD in terms of both time since diagnosis and age of the patients, with a lower dissociation Delta indicating a more advanced stage of AD. Ultimately, these data suggest that dissociated Abeta antibody levels are of significant diagnostic value at the onset of the neurodegenerative process and, thereafter, may be a useful biomarker for disease progression. Copyright 2009 Elsevier Inc. All rights reserved.