# Mechanisms of Functional Vascular Impairment In Genetic Models of Cerebral Small Vessel Disease

> **NIH NIH RF1** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $156,235

## Abstract

PROJECT SUMMARY
Vascular cognitive impairment (VCI) is any level of cognitive alteration that is attributable to cerebrovascular
pathologies. After Alzheimer disease, VCI is the second leading cause of dementia and accounts for ~15-30%
of all dementia cases. Cerebral small vessel disease (cSVD) accounts for up to 20% of all strokes and is the
most common pathology underlying VCI. Importantly, the pathogenesis of cSVD is incompletely understood
which represents a major barrier in developing therapies for the disease. Using genetic models of human
cSVD we have identified two potentially novel molecular mechanisms in different cell types that only manifest
in aged mice and that may contribute to progressive cSVD. Our data suggest that cSVD may represent a
mechanistically diverse collection of diseases that share similar endpoints and that investigation of multiple
disease models will be required to understand the full pathophysiological profile. Our interdisciplinary team of
experts will incorporate unique genetic resources, vascular pressure myography, patch-clamp
electrophysiology, calcium imaging, specialized magnetic resonance imaging modalities and learning and
memory behavior assays to 1) Develop and characterize multiple novel genetic models of cSVD using genes
that contribute to both familial and sporadic disease in humans 2) test a potential disease-modifying
intervention and functionally stratify potentially distinct classes of mutations and 3) compare the relative
contributions of different neurovascular unit cell types and address the extent to which defects are cell
autonomous or non-autonomous. Our long-term objective is to understand the heterogeneity underlying cSVD
and determine if there are convergent or overlapping pathways that might represent therapeutic targets for
mechanism-based interventions.

## Key facts

- **NIH application ID:** 10612694
- **Project number:** 3RF1NS110044-01S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Scott Earley
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $156,235
- **Award type:** 3
- **Project period:** 2022-06-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10612694

## Citation

> US National Institutes of Health, RePORTER application 10612694, Mechanisms of Functional Vascular Impairment In Genetic Models of Cerebral Small Vessel Disease (3RF1NS110044-01S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10612694. Licensed CC0.

---

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