Continued food allergen consumption exacerbates beta-amyloid accumulation in allergen-sensitized App NL-G-Fmice

Abstract

Abstract Alzheimer’s disease (AD) is the most common neurodegenerative disease, with β-amyloid (Aβ) plaque deposition being one of the hallmark pathologies. However, the etiology of AD remains elusive. While chronic inflammation from recurrent infections or injury seems to contribute to AD development, it is unclear whether atopic diseases, such as allergies, are associated with AD. We previously reported that continuous consumption of a whey protein (WP)-containing diet led to lasting neuroinflammation in C57BL/6J mice that were sensitized but tolerant to a bovine milk allergen, β-lactoglobulin (BLG; Bos d 5). Thus, we hypothesized that the persisting neuroinflammation due to repeated allergen consumption would exacerbate AD pathology over time in genetically predisposed, allergen-tolerant individuals. To address this hypothesis, we sensitized 1-month-old male and female transgenic App NL-G-Fknock-in mice to BLG and subsequently fed them either a whey-free control or a WP diet for 6 months. Despite their lack of overt allergic reactions, BLG-sensitized mice showed elevated plasma levels of BLG-specific IgE and IgG1. Leukocyte infiltration was observed in the hippocampus of sensitized mice, and WP-fed sham mice to a lesser extent. In contrast, mast cell accumulation was apparent in the dura of sensitized mice regardless of the diet. Importantly, Aβ plaque load and Aβ peptide levels were greater in the hippocampus of BLG-sensitized mice on the WP diet compared to the respective sham group. These results indicated that continuous allergen consumption exacerbated AD-like pathology in BLG-sensitized App NL-G-Fmice, suggesting that chronic food allergen exposure may promote the progression of AD in susceptible individuals. Supported by the National Institute of Health/National Institute on Aging (NIH/NIA) under grant number R21AG070412