P1‐085: Serum antibody biomarkers for Alzheimer's disease

Background: Because there is immune system activation in Alzheimer’s disease (AD), there may be serum antibodies that can serve as biomarkers for the disease. A novel unbiased approach to identifying disease-related antibodies, using combinatorial organic chemistry, involves the production of peptoid microarrays. Peptoids are oligo-N-substituted glycines which retain the binding characteristics of peptides, are easy to synthesize, and have been shown to be rich sources of protein ligands. Methods: Using a microarray consisting of 15,000 unique 8-mer peptoids, and serum from 6 AD, 6 Parkinson’s disease (PD) and 6 normal control subjects, we identified 3 peptoids that capture IgG antibodies whose levels are 3-10-fold higher in each AD patient compared to each PD and each normal control. Using a larger set of AD (49), PD (20) and normal controls (25), along with 10 MCI cases, we sought to validate the sensitivity and specificity of the 3 AD peptoids. Results: The 3 AD peptoids provide >90% sensitivity and specificity for the identification of AD. In addition, 9 of the 10 MCI cases showed elevated peptoid levels compared to normal controls. Conclusions: The peptoids should be useful biomarkers for AD, and for detecting the disease at an early time-point (i.e., MCI). Also, the antibodies recognized by the peptoids may represent novel drug targets for the treatment of the disease.