# Microvascular Network Degeneration in a Novel Mouse Model of Alzheimer's Disease and Cerebral Amyloid Angiopathy

> **NIH NIH R21** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2021 · $466,590

## Abstract

Abstract
Alzheimer’s disease is a burgeoning national epidemic and an effective treatment is urgently needed. It is now
widely recognized that vascular disease contributes to Alzheimer’s disease and, in some cases, may be central
to the process of neuronal degeneration. Cerebral amyloid angiopathy (CAA) is a vasculopathy produced when
β-amyloid forms a toxic encrustation on cerebral arterioles and capillaries; it independently contributes to
cognitive impairment and predisposes elderly patients to intracerebral hemorrhage. CAA has emerged as a
critical variable in the search for a treatment for Alzheimer’s disease, and is particularly important as
mechanisms of cerebral β-amyloid clearance are beginning to be better understood. Never-the-less,
fundamental mechanisms of whether and how β-amyloid undermines the structural integrity of vessels remain
unknown. We propose to optimize and study a new mouse model of CAA induced by surgically implanting
purified β-amyloid seeds isolated from human cerebral microvessels with CAA into the cerebral ventricles of
5xFAD mice. Previous animal models of CAA are inadequate due to slow development of β-amyloid pathology
and minimal development of microvascular degeneration, whereas the current model develops robust CAA
within 3 months of the injection along with other microvascular degeneration features. Our main goals are 1) to
optimize this model and 2) use it to definitively assess for a link between vascular β-amyloid deposition and
microvascular degeneration. We will evaluate for microvascular degeneration using advanced microscopy
techniques, including 3-dimensional mapping of the microvascular network using CLARITY and assessment of
the stiffness of the extracellular matrix in arterioles affected by CAA using atomic force microscopy. We will
also assess functional, neurobehavioral outcomes in this new model system. This work will answer
fundamental questions about the link between vascular integrity and Alzheimer’s disease and provide a
foundation for future work to better understand the molecular mechanisms of vascular fragility in CAA.

## Key facts

- **NIH application ID:** 10126622
- **Project number:** 1R21AG070859-01
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Matthew Schrag
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $466,590
- **Award type:** 1
- **Project period:** 2021-03-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10126622

## Citation

> US National Institutes of Health, RePORTER application 10126622, Microvascular Network Degeneration in a Novel Mouse Model of Alzheimer's Disease and Cerebral Amyloid Angiopathy (1R21AG070859-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10126622. Licensed CC0.

---

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