Absence of biomarkers has posed a formidable challenge in the development of effective treatment for Alzheimer disease (AD). Blood-based biomarkers could offer advantages that allow for early AD diagnosis and are critical in monitoring efficacy in clinical studies. Proposed studies aim to identify a set of novel blood biomarkers and examine their potential application as diagnostic agents. Phage display is a powerful approach to engineer peptides or proteins for binding to targets of interest. Therefore, we will apply phage display technology to identify peptides that selectively interact with molecules in AD blood samples, not in the age matched controls. In Aim 1, we will identify potential biomarkers by screening two libraries with a diversity of approximately 2 billion peptides against AD and control blood samples. To overcome the anticipated kinetic limitations with monovalent peptides, we will polymerize them by conjugation to dendrimers combined with functional moieties including fluorescent dyes for validation studies in Aim 2. These studies will identify a set of peptides that can be potentially used as diagnostic agents for AD. Furthermore, the proposed research is highly transformative and can be widely applied for biomarker studies in other human disorders. Overall, these proposed studies address a critical unmet medical need in AD by providing large sets of new biomarkers for rapid and accurate non-invasive diagnosis of AD using innovative approaches.
Discovery of Alzheimer’s Disease Blood Biomarkers Using Phage Display Technology
2013 to 2015
Funding to date:
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