Introduction: Diagnosis of Alzheimer's Disease (AD) currently relies heavily on clinical presentation and the biomarkers pTau217 and Aβ42. However, neuropathological pathogenesis can be initiated prior to clinical presentation which complicates the use of these biomarkers for personalized diagnosis and treatment. Through leveraging transcriptomic microglial signatures in the brain and transferring these signatures to blood, we sought to develop a transcriptomic plasma biomarker panel for early-stage diagnosis of AD based on microglial gene expression. In developing the gene panel, we used a variety of statistical methods to select the DEGs reflected in microglia and made a label transfer of diagnoses to transcriptomic data in blood. Methods: To identify whether the DEGs expressed in the selected microglial gene panels were represented in most recent GWAS studies, we conducted an analysis to determine if there was any overlap between the Bellenguez 2022 Alzheimer's Disease GWAS. We also conducted pathway analysis on the overlapping genes. Results: Using a panel of 300 genes, AUC for blood samples was 0.7 with strong accuracy to predict the AD class (75%) however accuracy to predict cognitively normal individuals was 53%. The accuracy and specificity of the 50 and 30 panels demonstrated better balance between prediction of the AD and normal classes (65-71%) with similar AUC (0.7) to the 300 gene panel. The 30 gene panel contained two GWAS genes: ELDR and PTDGR. The 50 gene panel included one gene: SERPINE1. The 300 gene panel contained 13 genes: CELF2, PICALM, ELMO1, ATP8B4, SORL1, TRIO, UBE2K, LUC7L3, RBM47, RASA1, JAZF1, HERC1 and CMIP. This set of genes is involved in multiple signaling pathways, including RHO GTPases, RAS GTPases, and MAP kinases, which are critical for cytoskeletal remodeling and cellular signaling. These genes are also involved in endocytosis, RNA splicing and neuron projection development. Conclusions: With the most substantial GWAS enrichment in the 300 gene panel, there is strong functional significance of genes associated with AD pathobiology. The findings demonstrate that the gene panels capture the genetic signals established in GWAS, supporting the robustness of our microglial gene panel for the blood-based transcriptomic biomarker. Symposium Presenter: Kenneth Vergel de Dios The Role of Cellular Adhesion in Non-stem Cell Tissue Repair in the

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