# PATHOBIOLOGICAL STUDIES OF VESSEL BACE1 IN CEREBROVASCULAR AMYLOID ANGIOPATHY

> **NIH NIH R01** · ROSKAMP INSTITUTE, INC. · 2020 · $400,000

## Abstract

Abstract
The incidence of Alzheimer disease (AD) with vascular degeneration is greatly increased following
cerebral hemorrhagic stroke in which cerebral amyloid angiopathy (CAA) occurs in affected brain
areas. The most common form of CAA is of the amyloid beta-peptide (Aβ) type. Aβ, which is derived
from the beta-amyloid precursor protein (APP) by sequential proteolytic cleavages from β-secretase
(BACE1) and -secretase, is widely believed to trigger a cascade of pathological events culminating in
AD including accompanied by degeneration of vascular cells: vascular smooth muscle cells (VSMCs),
vascular endothelial cells (VENCs) and pericytes. While extensive studies on pericytes in CAA have
been performed, multiple studies demonstrated that an increasing accumulation of A in the vessel
basement membrane is associated with the degeneration of adjacent VSMCs and VENCs.
Importantly, our recent preliminary data showed that cerebral vascular cells from human CAA brains
express high levels of β-secretase (BACE1). However, what causes vascular degeneration or death
in CAA remains unclear. We recently reported that a cell death receptor, TNFRI, is required for Aβ-
induced cell death and depletion of TNFRI reduced BACE1. In this application, we will study whether
and how BACE1 can be up-regulated in vascular cells and what molecular mechanisms of BACE1
elevation causes cerebral vascular cell death in our new mouse models of AD related CAA. The
ultimate goal of this proposal will not only advance our understanding the mechanisms of CAA-
induced hemorrhage but, also to, in principle, identify novel therapeutic targets and offer novel alert
for potential side effects of BACE1 inhibitors in patients with Alzheimer’s disease accompanying
vascular degeneration.
Key words: BACE1, TNF inflammation, animal models, neurodegeneration

## Key facts

- **NIH application ID:** 10022165
- **Project number:** 5R01NS092610-05
- **Recipient organization:** ROSKAMP INSTITUTE, INC.
- **Principal Investigator:** FIONA C. CRAWFORD
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $400,000
- **Award type:** 5
- **Project period:** 2016-09-30 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10022165

## Citation

> US National Institutes of Health, RePORTER application 10022165, PATHOBIOLOGICAL STUDIES OF VESSEL BACE1 IN CEREBROVASCULAR AMYLOID ANGIOPATHY (5R01NS092610-05). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10022165. Licensed CC0.

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