Application of Immunosignatures to the Assessment of Alzheimer's Disease

作者：Restrepo Lucas; Stafford Phillip; Magee D Mitch; Johnston Stephen Albert^*

来源：Annals of Neurology, 2011, 70(2): 286-295.

DOI：10.1002/ana.22405

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 A beta peptide and blocking protocols, we demonstrate that most of this signature is not due to the subject's antibodies raised against A beta.
Interpretation: We propose that "immunosignaturing" technology may have potential as a diagnostic tool in AD. ANN NEUROL 2011;70:286-295

• 出版日期2011-8