330 Dietary lactoferrin supplementation mitigates age-related proteomic changes in the cortex of aged heterogenous mice

Objectives/Goals: The main objective of this study was to determine if dietary supplementation with the iron-binding protein lactoferrin is able to reverse age-related brain proteomic changes in a heterogenous mouse model of aging, with implications for the modulation of age-related brain disease. Methods/Study Population: UM-HET3 mice of both sexes were aged to 6 months on control chow (Young Control, N=11) or 24 months (Old Control, N=12) on control chow or a diet supplemented with 12,000 ppm of bovine lactoferrin for 9.5 weeks before sacrifice (Old Lactoferrin, N=13). At sacrifice, brain cortex was collected. Cortex homogenate was analyzed through SomaLogic for 1,500 specific proteins relevant to brain aging. Differential expression analysis was run to analyze the age and treatment effect separately, with an adjusted p-value cutoff of 0.05 to reveal effects of age (young control vs old control) and treatment (old control vs old lactoferrin) separately. Gene Ontology Biological Processes (GO-BP) Enriched Pathway analysis was run to identify the biological pathways altered by lactoferrin supplementation. Results/Anticipated Results: Differential expression analysis adjusted by sex identified 71 differentially expressed proteins in the age comparison and 99 differentially expressed proteins in the treatment comparison. Thirteen proteins were differentially expressed in both lists, which we classify as lactoferrin rescued proteins, those that were elevated in old untreated mice, but significantly lowered by treatment. These proteins include SYDC, CLIC5, NF2L2, STAT3, Peroxiredoxin.3, UFM1, Profilin.1, NUCB1, Laminin.2, Ezrin, PPT1, IDH, and PUR9. Pathway analysis revealed significant alteration in 30 pathways relevant to synapse, neuron, and cellular structure and function relevant to age-related neurodegenerative disease. Discussion/Significance of Impact: Lactoferrin may be a viable therapy for the modulation of age-related brain changes. Next, we will evaluate endogenous levels of lactoferrin as a biomarker for Alzheimer’s disease, moving toward a clinical trial to evaluate the utility of lactoferrin to serve as both a biomarker and intervention against age-related neurodegenerative disease.