# A microphysiological model of the brain-lymphatic system in Alzheimer's disease

> **NIH NIH R21** · VIRGINIA POLYTECHNIC INST AND ST UNIV · 2024 · $239,758

## Abstract

Summary
The nervous system interacts with the immune system in ways that have been identified to contribute to a number
of diseases, including Alzheimer’s disease, infection, brain cancer, and multiple sclerosis. The field of
neuroimmunology is a quickly growing research area that involves complex models and manipulations, most
often using in vivo models in mice. These models, though useful, lack human components, and have the added
difficulties of complex manipulations, difficulty in modulating individual organs without affecting others, and
difficulty in the acquisition of dynamic data. In contast, organ-on-chip systems offer benefits in these areas as
well as flexibility of cellular components and experimental conditions, but have rarely been applied to
neuroimmunology beyond models of the blood-brain barrier. Here we propose to develop a microphysiological
system that recapitulates the brain-meninges-lymph node axis in both healthy conditions and in a model
Alzheimer’s disease. To do so, we will integrate three tissue engineered models recently established in our
laboratory – of the human brain, lymph node, and meninges – into a user-friendly microfluidic device for media
recirculation, and validate the function of each compartment separately and together. We will deliberately retain
modularity of the system, so that we can examine the interactions of these components while easily manipulating
single organ compartments with fluid flow, drugs, mutations, or disease states. We will characterize the response
of each component to fluid flow, enable T cell circulation between organs, and test the response to inflammation
of each component separately and together. Next, we will convert the baseline model into an Alzheimer’s specific
model by incorporating a suite of tissue engineered models of Alzheimer’s brain, derived from neural stem cells
from individual Alzheimer’s patients. After confirming lymphatic drainage of amyloid similar to what has been
shown in vivo, we will quantify the impact of the Alzheimer’s brain on the inflammatory state of the meninges and
draining lymph node compartments, and determine the physical and chemical requirements for biomimetic T cell
migration into and within the brain. If successful, we will have both a baseline “normal” system linked through
multiple compartments and created from all-human components, poised as a foundation for future use across
neuroimmunological research, and a model of interactions between the brain, meninges, and cervical lymph
nodes in Alzheimer’s Disease. Ultimately, we envision using these systems for mechanistic tests of disease
onset and progression, as well as to test variations in drug responses between individuals of varied ancestry,
sex, and age, by sourcing cells from patients representative of different cohorts.

## Key facts

- **NIH application ID:** 10871094
- **Project number:** 1R21AG086857-01
- **Recipient organization:** VIRGINIA POLYTECHNIC INST AND ST UNIV
- **Principal Investigator:** Jennifer M Munson
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $239,758
- **Award type:** 1
- **Project period:** 2024-09-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10871094

## Citation

> US National Institutes of Health, RePORTER application 10871094, A microphysiological model of the brain-lymphatic system in Alzheimer's disease (1R21AG086857-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10871094. Licensed CC0.

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