# Impact of APOE on endothelial cell proteomes in Alzheimer's disease

> **NIH NIH F32** · EMORY UNIVERSITY · 2023 · $76,292

## Abstract

ABSTRACT (PROJECT SUMMARY)
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that results in deposition of amyloid-b
(Ab) peptide in brain parenchyma and cerebral blood vessels as cerebral amyloid angiopathy (CAA). Genome-
wide association studies (GWAS) have identified numerous genes altering AD risk with the e4 allele of
apolipoprotein E (APOE4) showing the strongest association with AD and CAA. APOE4 modulates amyloid
accumulation in cerebrovasculature and impacts the efficiency of Ab clearance from the brain. In addition,
APOE4 carriers exhibit accelerated breakdown of the blood-brain barrier (BBB) and higher risk for
cerebrovascular dysfunction during normal aging. However, the underlying mechanisms of this genetic
susceptibility on cerebrovascular function and pathology are still poorly understood. Recent work from our group
revealed APOE-driven protein perturbations associated with endothelial cells in the postmortem brain tissue from
AD individuals. Yet, these observations come from bulk brain tissue limiting the ability to dissect cell-type specific
proteomic changes. Thus, the major goal of this proposal is to molecularly define the endothelial cells in the
context of APOE-associated amyloidosis. I hypothesize that APOE4 genotype directly impacts endothelial
proteome leading to the BBB dysfunction and breakdown. In Aim 1, I will perform an unbiased proteomic analysis
of isolated cerebral blood vessels from cortical tissues of AD, AD with severe CAA, asymptomatic AD (AsymAD,
individuals exhibiting amyloid and tau accumulation in the brain with no cognitive decline), and non-demented
control individuals. I will further apply integrative analysis to the brain vascular proteomes and previously
generated proteomic data of cerebrospinal fluid (CSF) to identify AD CSF biomarkers that mirror pathological
changes of the cerebrovasculature. In Aim 2, I will explore in vivo effect of APOE and amyloid on endothelial cell
proteome by taking advantage of highly innovative, recently developed by our group approach that allows for
Cell-type specific In-vivo Biotinylation of Proteins followed by mass-spectrometry (CIBOP-MS). Dissecting
proteomes of endothelial cells in a disease setting will be a conceptual advancement and a crucial step towards
understanding the mechanisms underlying AD-related BBB breakdown, diminished blood flow, and pathological
accumulation of amyloid in the cerebrovasculature.

## Key facts

- **NIH application ID:** 10606847
- **Project number:** 1F32AG081135-01
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Aleksandra Maria Wojtas
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $76,292
- **Award type:** 1
- **Project period:** 2023-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10606847

## Citation

> US National Institutes of Health, RePORTER application 10606847, Impact of APOE on endothelial cell proteomes in Alzheimer's disease (1F32AG081135-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10606847. Licensed CC0.

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