Objectives/Goals: Neurodegenerative diseases involve progressive neuronal loss or dysfunction, often due to accumulated damage and impaired repair mechanisms. Our research evaluates the role of innate immune recognition proteins to provide insights into age-related neurodegeneration and cognitive decline. Methods/Study Population: We will utilize transcriptomic data from the Long-Life Family Study (LLFS), a cohort rich in genetic and phenotypic data related to aging and longevity. Our approach includes assessing a set of innate immune recognition proteins, also known as pattern recognition receptors (PRRs) expression across various age groups, focusing on potential correlations with cognitive performance. By analyzing serum transcriptomic profiles, we aim to map changes in expression and DNA repair genes over time, evaluating their connection to cognitive health and neurodegeneration in aging populations. Results/Anticipated Results: We anticipate that the expression of some PRRs will increase with age and correlate with cognitive decline, suggesting a role in age-related neurodegeneration. We also expect a decrease in DNA repair pathway gene expression in older age groups, contrasting with an increase in genes involved in endogenous DNA detection. These results will reveal how PRRs may function as neuroprotective factors and how their expression changes may relate to the decline in DNA repair processes with age, providing a better understanding of innate immune recognition in cognitive health. Discussion/Significance of Impact: This study will reveal the role of PRRs in aging and neurodegeneration, potentially establishing them as a key player in neuronal protection. Findings may guide future research into therapeutic strategies targeting them for Alzheimer’s and other age-related neurodegenerative diseases.