# Neuroprotective Effects of Vascular Endothelial Growth Factor in Alzheimer's Disease

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2021 · $837,506

## Abstract

Abstract
Vascular endothelial growth factor (VEGF) is a protein that has been implicated in protection against
Alzheimer's disease (AD). High levels of cerebrospinal fluid (CSF) VEGF are associated with slower rates of
cognitive decline and slower rates of brain atrophy. Furthermore, the neuroprotective effects of VEGF are
particularly strong among individuals who are harboring high levels of AD neuropathology, suggesting VEGF
may protect against the clinical consequences of AD. Indeed, when treating the hippocampus of AD mice with
stem cells expression VEGF, the memory deficits associated with AD are reversed. Yet, the development of
VEGF as a therapeutic target has been limited due to the large number of biological process impacted by
VEGF signaling. The VEGF family consists of 5 ligand genes, 3 known tyrosine-kinase receptor genes, and 2
modulating receptor (neuropilins) genes. Interactions between this diverse set of ligands and receptors drive
vastly different signaling cascades. Such biological variation provides an exciting opportunity to interrogate the
various VEGF pathways through targeted genomics and proteomics. This proposal will seek to identify the
VEGF signaling molecules that most strongly predict neuroprotection, and clarify the pathways that underly the
beneficial effects of VEGF. We will leverage advanced genomic and proteomic approaches using human
samples from well characterized longitudinal cohort studies of aging, with a particular focus on gene and
protein expression in brain tissue. Our multi-disciplinary team is uniquely positioned to perform this detailed
analysis of VEGF signaling by leveraging the Resilience from Alzheimer's Disease (RAD) database, which
includes a harmonized and validated continuous metric of resilience across 8 large cohort studies of AD. In
RAD, we have quantified the degree to which an individual is resilient to the cognitive deficits associated with
AD neuropathology, providing the ideal phenotype to evaluate the effects of VEGF. The RAD includes
genotype data (n=3037), gene expression data from brain tissue (n=588), and access to stored brain tissue for
novel proteomic analyses (n=1433). This proposal will first perform a comprehensive analysis of VEGF ligand
and receptor genes in brain tissue to identify which gene isoforms mostly strongly relate to resilience. Second,
we will perform a detailed proteomic analysis in which we perform comprehensive measurement of all VEGF
ligand and receptor proteoforms, including post-translational modifications, to clarify VEGF effects in brain at
the protein level. Finally, we will leverage the rich VEGF signaling data generated from this proposal to identify
additional genetic markers of resilience that fall along this same signaling pathway. Knowledge about the
mechanisms, signaling pathways, and specific forms of VEGF that most strongly predict resilience will
accelerate the development of VEGF signaling molecules as targets for pharmacological interventi...

## Key facts

- **NIH application ID:** 10107737
- **Project number:** 5R01AG061518-03
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Timothy J Hohman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $837,506
- **Award type:** 5
- **Project period:** 2019-03-15 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10107737

## Citation

> US National Institutes of Health, RePORTER application 10107737, Neuroprotective Effects of Vascular Endothelial Growth Factor in Alzheimer's Disease (5R01AG061518-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10107737. Licensed CC0.

---

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