Nagamoto-Combs Named PI on NIH Grant
Kumi Nagamoto-Combs, assistant professor with UND's Biomedical Sciences Department, has been funded with an R21 grant from the National Institutes of Health (NIH). The title of this award is "Investigation of chronic allergen exposure as a risk factor for Alzheimer's disease."
The project addresses the Continued consumption of food allergens by mildly allergic individuals may increase the risk for Alzheimer’s disease (AD) and other neurodegenerative disorders via chronic intestinal, systemic, and brain inflammation. Longer durations of allergen consumption, aging and genetic predispositions may further potentiate the risk. In this project, we aim to determine whether consistent intestinal insults with a food allergen contribute to the progression of AD-like pathology in a mildly food-allergic mice, and whether the duration of allergen exposure and age of mice are additional factors for exacerbating AD-like symptoms in Alzheimer’s mouse model.
"The etiology of Alzheimer’s disease (AD) is elusive. Chronic systemic inflammation has been implicated in the development of AD-associated neurodegenerative conditions through dysregulation of neuroinflammation. Although severe injuries and recurrent infections are likely triggers of prolonged immune activation, atopic diseases, such as food allergy, asthma, and eczema, also cause chronic systemic inflammation and may contribute to the development of AD pathology, especially when the diseases are not controlled properly. Mildly allergic individuals do not always display severely uncomfortable or life-threatening reactions, and therefore may inadvertently expose themselves to offending allergens repeatedly by being unaware of their hypersensitivities or unconcerned with allergen avoidance. Thus, we hypothesize that chronic allergen exposure consumption by mildly allergic individuals potentiates the risk for development or progression of AD-related pathology via sustained systemic inflammation. While clinical studies have shown that atopic diseases, particularly eczema, are associated with AD, the link between food allergy and AD has not been fully addressed. In this proposed project, we will test our hypothesis using our mouse model of non-anaphylactic mild cow’s milk allergy (mCMA), in which C57BL/6J mice are sensitized to a whey protein, β-lactoglobulin (BLG). We have previously shown that BLG-sensitized mice develop peripheral and central inflammation with induced serum levels of BLG-specific IgE and IgG1, despite the lack of overt allergic reactions upon challenge. Moreover, these mCMA mice are able to eat allergen-containing food without displaying detectable physical symptoms or taste aversion, serving as an excellent model to simulate mildly allergic individuals with continued exposure to the offending allergen. Using this experimental mCMA paradigm on wild-type C57BL/6J strain and a transgenic AD mouse model, the AppNL-G-F strain, we will first determine whether the extent of intestinal and systemic inflammation is exacerbated by chronic allergen exposure in a duration- and age- dependent manner (Aim 1). We will further examine whether continued feeding of allergen-containing food will potentiate decline in cognitive behavior and exacerbate AD-like neuropathology (Aim 2). The outcomes of this study will investigate food allergy with chronic allergen exposure as a risk factor for AD and may offer a novel strategy to prevent or slow the progression of disease."