Project Summary The long-term goal of this study is to develop a biomarker-based screening assay for the detection of AD-related biochemical changes that can be measured in biofluids such as blood or CSF. The main goal of this study is to identify phage-based probes to protein post-translational modifications (PTMs) of tau that are associated with AD and its progression. This study will have multiple positive effects, including more accurate diagnosis and improved ability to monitor disease progression. To accomplish this goal, the project has one aim: Aim. Identify phage with high sensitivity and specificity for AD-related PTMs to the tau protein in blood and CSF. Preliminary data from the previous grant demonstrated the proposed method could differentially identify tau PTMs and differentiate between a pilot group of clinically diagnosed AD and Control subjects in CSF. The current project aims to validate these findings in a larger cohort of subjects, and extend the work into blood testing. AD diagnosis occurs relatively late in the disease process, and many AD cases are misdiagnosed. This proposal addresses a significant gap in developing robust biomarker arrays to assist in the more accurate detection of AD-related dementia. Completing this study would be the next step to creating a PTM-based array of tau PTMs to improve further the accuracy of diagnosis and monitoring of disease progression.