# Investigation of chronic allergen exposure as a risk factor for Alzheimer's disease

> **NIH NIH R21** · UNIVERSITY OF NORTH DAKOTA · 2020 · $387,750

## Abstract

Project Summary/Abstract
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.

## Key facts

- **NIH application ID:** 10108874
- **Project number:** 1R21AG070412-01
- **Recipient organization:** UNIVERSITY OF NORTH DAKOTA
- **Principal Investigator:** Kumi Nagamoto-Combs
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $387,750
- **Award type:** 1
- **Project period:** 2020-09-11 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10108874

## Citation

> US National Institutes of Health, RePORTER application 10108874, Investigation of chronic allergen exposure as a risk factor for Alzheimer's disease (1R21AG070412-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10108874. Licensed CC0.

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