# Development of 3D vascularized model of Blood Brain Barrier and its application to Alzheimer disease research

> **NIH NIH R21** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2020 · $200,500

## Abstract

SUMMARY
As the population grows older, the demand for improved methods to study cerebrovascular diseases has rapidly
increased. At the same time, there has been burgeoning interest in reproducing physiological properties of blood-
brain-barrier (BBB) in vitro that can be helpful in both basic and clinical studies. A need therefore exists for
standardized models as tools to help scientists better understand the physiological and pathological mechanisms
involved in cerebrovascular diseases, including Alzheimer’s disease (AD). The proposed studies are aimed at
developing a versatile BBB model that recapitulates BBB microvascular networks (µVNs) in a three dimensional
(3D) microfluidic platform, and apply this model to AD pathogenesis research. Building on our extensive set of
preliminary and related data, we propose to recreate 3D AD-BBB µVNs within extracellular matrix (ECM)
scaffolds that enable intercellular signaling and exposure to biochemical gradients in a well-defined
microenvironment.
AD is a progressive neurodegenerative disease which is characterized by deterioration of cognitive function and
deposition of β-amyloid (Aβ) peptides. We previously reported that human neural progenitor cells overexpressing
Familial AD (FAD) mutations in the amyloid-β precursor protein (APP) and presenilin 1 (PSEN1) genes grown in
a 3D culture system successfully recapitulate AD pathologies (3D AD culture model). However, this model lacks
BBB components, which are critical to neurological function and AD pathogenesis. We will develop 3D-
differentiated AD cells in a 3D microfluidic platform in the presence of the BBB µVNs (3D AD-BBB µVN model).
We will investigate how the BBB is disrupted in AD and whether optimizing the BBB can ameliorate AD
progression. Our 3D AD-BBB µVN model will be useful for both BBB-related disease pathogenic cascades, such
as AD, and drug discovery in a human brain-like environment.

## Key facts

- **NIH application ID:** 10016386
- **Project number:** 5R21NS105027-02
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** ROGER D KAMM
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $200,500
- **Award type:** 5
- **Project period:** 2019-09-15 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10016386

## Citation

> US National Institutes of Health, RePORTER application 10016386, Development of 3D vascularized model of Blood Brain Barrier and its application to Alzheimer disease research (5R21NS105027-02). Retrieved via AI Analytics 2026-06-25 from https://api.ai-analytics.org/grant/nih/10016386. Licensed CC0.

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