# iPSC-derived neurovascular tissue model of cerebral amyloiad angiopathy

> **NIH NIH R61** · VANDERBILT UNIVERSITY · 2020 · $831,660

## Abstract

Project Summary
Cerebral amyloid angiopathy (CAA) is caused by the formation of beta amyloid plaques on cerebral arteries,
which leads to loss of smooth muscle, vascular fragility, and intracranial hemorrhage. CAA is a risk factor for
dementia independent of Alzheimer's Disease (AD), and similar to AD, no treatments are available to reverse or
mitigate disease pathology. This lack of therapeutic avenues stems in part from inadequate model systems
available to study the disease and identify treatment strategies. While transgenic mice have been engineered to
develop certain aspects of CAA, no animal fully recapitulates the disease phenotype. Moreover, most animal
models take over a year to develop the disease, and generally owing to the nature of in vivo systems, only a
limited number of assays can be conducted to test drug efficacy and stratify treatment regimens. Therefore, to
provide a robust, complementary resource for drug development, this proposed project focuses on constructing
an in vitro human neurovascular model of CAA. This model will build upon our previous advancements in
incorporating human induced pluripotent stem cell (iPSC)-derived neurovascular progenies into three-
dimensional tissue constructs with representative function and appropriate spatial organization. We also
introduce a novel concept for controlling CAA onset and progression using pre-templated oligomer seeds
embedded in the tissue construct and a precisely delivered exogenous source of beta amyloid monomer. Aim 1
will explore concentrations of embedded oligomers and exogenous monomer to establish the kinetics of vascular
amyloid deposition in acellular hydrogels. Aim 2 will incorporate relevant neurovascular cell types into the system
and assess CAA pathology onset and progression under parameters established in Aim 1. Aim 3 will benchmark
the observed in vitro pathology against a relevant mouse model and human tissue from CAA patients. Overall,
if the in vitro system can recapitulate CAA phenotypes and reproducibly model the time course of disease
progression, it will provide substantial value to the scientific community as a resource for identifying and testing
drugs that will ultimately treat this devastating neurodegenerative condition.

## Key facts

- **NIH application ID:** 10044329
- **Project number:** 1R61NS112445-01A1
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Ethan Lippmann
- **Activity code:** R61 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $831,660
- **Award type:** 1
- **Project period:** 2020-09-30 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10044329

## Citation

> US National Institutes of Health, RePORTER application 10044329, iPSC-derived neurovascular tissue model of cerebral amyloiad angiopathy (1R61NS112445-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10044329. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*