# Integrative analysis of multi-omics data to delineate CCL2 associated inflammatory pathways in Alzheimers Disease

> **NIH NIH R03** · CLEVELAND CLINIC LERNER COM-CWRU · 2021 · $161,000

## Abstract

PROJECT SUMMARY/ABSTRACT
Alzheimer's disease (AD) is the most common cause of dementia worldwide. In the US, it is the fifth leading
cause of death in people over 65 years of age. Delineating factors that predict rate of future cognitive decline
and dementia are important but are yet to be thoroughly understood. Knowledge of disease progression related
biological factors will be critical in designing novel therapeutic strategies to mitigate their deleterious effects and
thereby prevent the associated cognitive and behavioral decline.
The research at the foundation of this R03 is a clinical translational study that uses systems biology and
bioinformatics techniques to characterize the genetic and cellular context of dysregulated inflammatory pathways
in the brain and periphery that impact longitudinal cognitive decline in different stage of Alzheimer's disease. Our
earlier work among clinical patients at the Mild cognitive impairment stage AD suggests that a clinically
meaningful degree of rapid cognitive decline was best predicted by baseline levels of an inflammatory analyte
CCL2. In this work we hope to extend this initial insight by characterizing in depth the genetic drivers behind the
inflammatory deregulation in clinical AD and the cellular context in which it occurs in the periphery and the central
nervous system. We will confirm and validate these changes with genome wide (RNA-seq) expression changes
and against data from other large national data (ADNI, Accelerating Medicines Partnership-AD) and by single
cell transcriptomics of immune cells in the cerebrospinal fluid among well characterized patients. If the hypothesis
and models are validated, scientific insights from this research will help identify novel therapeutic targets and
individual propensities for deleterious inflammatory responses for future precision medicine interventions against
neuroinflammation in AD to prevent disease progression and cognitive decline. If the hypothesis is found to be
not true, the findings from this study will still represent a significant advance in our knowledge of variability in
individual propensities to have a neuroinflammatory response in the face of neurodegenerative disease
pathology. The results of this will be useful both clinically and in designing and interpreting future research
outcomes.

## Key facts

- **NIH application ID:** 10109195
- **Project number:** 1R03AG070477-01
- **Recipient organization:** CLEVELAND CLINIC LERNER COM-CWRU
- **Principal Investigator:** Gurkan Bebek
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $161,000
- **Award type:** 1
- **Project period:** 2021-03-15 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10109195

## Citation

> US National Institutes of Health, RePORTER application 10109195, Integrative analysis of multi-omics data to delineate CCL2 associated inflammatory pathways in Alzheimers Disease (1R03AG070477-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10109195. Licensed CC0.

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