The discovery of serum biomarkers for Alzheimer's disease (AD) represents an enormous unmet medical need. This project will further explore the hypothesis that the adaptive immune system might react to unusual antigens produced as a result of AD pathology and as a result produce high levels of antibodies that would not be found in a normal individual. There is some evidence that this is the case. To discover these antibodies we plan to screen large libraries of bead-displayed synthetic oligomers and find compounds that retain far more antibodies from AD serum samples than from controls. These molecules would be employed as first generation capture agents for the AD-specific antibodies in a multiplexed Luminex-like diagnostic assay. If this R21 preliminary investigation is successful, it would set the stage for compound optimization and a much larger validation trial that could lead to an effective blood test for AD.
The development of a blood test for the diagnosis of Alzheimer's disease (AD) represents a major unmet medical need. The goal of this project will be to discover antibodies unique to AD patients and develop a blood test with which to quantify them. This will be done through the discovery of novel synthetic molecules that bind to these antibodies with high affinity and selectivity.
Erharuyi, Osayemwenre; Simanski, Scott; McEnaney, Patrick J et al. (2018) Screening one bead one compound libraries against serum using a flow cytometer: Determination of the minimum antibody concentration required for ligand discovery. Bioorg Med Chem Lett 28:2773-2778 |
Doran, Todd M; Sarkar, Mohosin; Kodadek, Thomas (2016) Chemical Tools To Monitor and Manipulate Adaptive Immune Responses. J Am Chem Soc 138:6076-94 |
Wu, Hao; Mousseau, Guillaume; Mediouni, Sonia et al. (2016) Cell-Permeable Peptides Containing Cycloalanine Residues. Angew Chem Int Ed Engl 55:12637-42 |
Doran, Todd M; Morimoto, Jumpei; Simanski, Scott et al. (2016) Discovery of Phosphorylated Peripherin as a Major Humoral Autoantigen in Type 1 Diabetes Mellitus. Cell Chem Biol 23:618-628 |