# Investigating the relationship of genetic, microbial, and intestinal inflammatory biomarkers in PD pathogenesis

> **NIH NIH P20** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2021 · $157,969

## Abstract

Parkinson’s disease (PD) is the second most common neurodegenerative disease worldwide. Currently, no
available therapies alter the underlying neurodegenerative process, and only symptomatic therapies can
improve patient quality of life. This may be in part attributable to the fact that different PD subtypes require
distinct therapies, indicating a substantial unmet need for more effective personalized therapies that are based
on disease etiology. A combination of genetic and inflammatory biomarkers may offer an avenue toward the
dissecting PD heterogeneity. There is growing appreciation for the role of chronic inflammation in pathogenesis
of PD. Specifically, an increased incidence of PD in patients with inflammatory bowel disease (IBD), a chronic
disease of the gut, has been reported world-wide. Our prior work strongly implicated coding PD-related LRRK2
mutations in the pathogenesis of IBD. We also showed that selective LRRK2 inhibitors have ameliorated
experimental colitis and reduced inflammatory cytokine TNF-α levels, a hallmark of IBD-associated
inflammation, in dendritic cells of IBD patients. The link between intestinal inflammation and PD is also
endorsed by elevated markers of intestinal inflammation and pro-inflammatory gut microbiota composition in
PD patients, suggesting that dysregulated signaling pathways of the gut immune system could explain the
susceptibility to certain subtypes of PD. However, even though reducing inflammatory processes has been
suggested as promising interventional goal for PD, no causal biological pathways have been identified to allow
for developing novel, or repurposing existing, drug targets. Therefore, the goal of this study is to detect to what
extent intestinal inflammation contributes to the development of PD and identify subtypes of PD based on the
levels of genetic susceptibility to intestinal immune dysregulation. Our specific aims are: 1) To determine the
relationship between intestinal biomarkers and gut microbiome diversity in patients with PD, IBD or controls by
comparing fecal calprotectin, a sensitive marker of intestinal inflammation, and stool bacterial diversity between
the disease and control groups; 2) Interrogate α-synuclein levels, LRRK2 expression and LRRK2-mediated
phosphorylation of target protein in the intestinal tissue of patients with IBD, PD and controls, and 3)
Characterize PD patients with high genetically-determined inflammatory burden in terms of their age of onset,
motor and non-motor symptoms, disease progression, response to drugs, and comorbidities using polygenic
risk scores (PRS) for various intestinal inflammatory conditions calculated in large existing PD datasets. We
will identify the biological pathways shared between PD and immune-mediated diseases. The proposed
studies will help better understand the role of intestinal inflammation in PD pathogenesis. In addition, they will
help establish an infrastructure for successful patient recruitment and sample collection ...

## Key facts

- **NIH application ID:** 10284436
- **Project number:** 1P20NS123220-01
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Inga Peter
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $157,969
- **Award type:** 1
- **Project period:** 2021-09-15 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10284436

## Citation

> US National Institutes of Health, RePORTER application 10284436, Investigating the relationship of genetic, microbial, and intestinal inflammatory biomarkers in PD pathogenesis (1P20NS123220-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10284436. Licensed CC0.

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