# Developing Biomarkers of Parkinson’s Disease Inflammation Using a Network Proteomics Approach

> **NIH NIH R21** · EMORY UNIVERSITY · 2021 · $430,270

## Abstract

ABSTRACT
Increasing evidence indicates that neuroinflammation is not a simple consequence of neurodegeneration in
Parkinson’s disease (PD), but an active process in disease progression. Thus, biomarkers capable of detecting,
staging, and monitoring alterations in these pathways promise to significantly advance PD therapeutics. We
recently developed a proteomic pipeline that leverages innovative network-based strategies to identify panels of
cerebrospinal fluid (CSF) biomarkers reflective of brain-based pathophysiology in neurodegenerative disease,
including inflammatory and immune-mediated processes. The application of this approach to the brain and CSF
proteomes of Alzheimer’s disease (AD) yielded highly reproducible, disease-specific CSF panels of biomarkers
linked to glial-mediated inflammation, endothelial humoral immunity, and myelin dysfunction. We hypothesize
that PD similarly features unique protein signatures in CSF reflective of brain-based neuroinflammation and
immune-mediated degeneration. Thus, we propose to utilize this network proteomics strategy to identify and
validate promising CSF biomarkers of PD neuroinflammation. Aim 1 will comprise an unbiased network analysis
of regional inflammatory dysfunction in the PD brain proteome, delineating protein alterations linked to
immune-mediated processes in vulnerable regions. This network-based analysis will help unravel the
complexities of inflammatory biology in the PD brain, distinguishing cell types (e.g., microglial, astrocytic,
endothelial) and functional properties (e.g., humoral, innate, pro- or anti-inflammatory) significantly associated
with disease. In Aim 2, we will then integrate these results with differential expression analysis of the PD CSF
proteome to identify CSF biomarkers with links to these brain-based inflammatory pathways. We will prioritize
biomarkers for further validation based on robustness and reproducibility of PD differential expression, disease-
specificity for PD, strength of association with brain-based inflammation, and ease of detectability using high-
throughput MS strategies. Future directions will include large-scale targeted MS validation of these prioritized
biomarkers with the overarching goal of developing a multiplex assay of PD inflammation that can be used to
diagnostically profile patients, monitor disease progression, individualize therapeutic strategies, and confirm
drug target engagement.

## Key facts

- **NIH application ID:** 10289028
- **Project number:** 1R21NS123882-01
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Lenora Higginbotham
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $430,270
- **Award type:** 1
- **Project period:** 2021-07-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10289028

## Citation

> US National Institutes of Health, RePORTER application 10289028, Developing Biomarkers of Parkinson’s Disease Inflammation Using a Network Proteomics Approach (1R21NS123882-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10289028. Licensed CC0.

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