Application of immunosignatures to the assessment of Alzheimer's disease

Objective: Accurate assessment of Alzheimer's disease (AD), both presymptomatically and at different disease stages, will become increasingly important with the expanding elderly population. There are a number of indications that the immune system is engaged in AD. Here we explore the ability of an antibody-profiling technology to characterize AD and screen for peptides that may be used for a simple diagnostic test. Methods: We developed an array-based system to profile the antibody repertoire of transgenic mice with cerebral amyloidosis (TG) and elderly individuals with or without AD. The array consists of 10,000 random sequence peptides (20-mers) capable of detecting antibody binding patterns, allowing the identification of peptides that mimic epitopes targeted by a donor's serum. Results: TG mice exhibited a distinct immunoprofile compared to nontransgenic littermates. Further, we show that dementia patients, including autopsy-confirmed AD subjects, have distinguishable profiles compared to age-matched nondemented people. Using antibodies to different forms of Aβ peptide and blocking protocols, we demonstrate that most of this signature is not due to the subject's antibodies raised against Aβ. Interpretation: We propose that "immunosignaturing" technology may have potential as a diagnostic tool in AD.