Whey protein consumption exacerbates beta-amyloid pathology in AppNL-G-F mice with subclinical milk allergy 3724

Abstract Description Alzheimer’s disease (AD) pathology is characterized by the accumulation of β-amyloid (Aβ) plaques in the brain and neuroinflammation, which can be reproduced in transgenic AppNL-G-F knock-in mice. We previously reported that C57BL/6J mice that were sensitized but tolerant to a bovine milk allergen, β-lactoglobulin (BLG; Bos d 5), showed lasting neuroinflammation after feeding on a whey-protein-containing diet (WP). Based on this finding, we hypothesized that chronic inflammation due to prolonged allergen consumption by subclinically sensitized individuals would exacerbate the development of genetically predisposed AD-related pathologies. To test this hypothesis, male and female AppNL-G-F mice were sensitized to BLG, and Aβ plaque load in the brain was examined after WP diet consumption for 3 or 6 months. Despite the development of allergen tolerance, evident from decreased BLG-specific IgE levels with the WP diet, increased Aβ levels were found in sensitized mice of both sexes after 6 months, indicating that sensitization alone was sufficient to exacerbate Aβ pathology. Importantly, the WP diet further elevated the Aβ levels. These results suggest that continued allergen consumption, as in oral immunotherapy, may have unexpected outcomes on the progression of AD in genetically predisposed individuals. Further characterization of neuroimmune responses may help define the mechanisms resulting in observed Aβ-related changes. Funding Sources Supported by NIH/NIA 1R21AG070412 to KNC; Histological services were provided by the UND Histology Core Facility supported by NIH/HIGMS awards P20GM113123, U54GM128729, and UND School of Medicine & Health Sciences Topic Categories Neuroimmunology (NEUR)