# Role of CSF microglia in health and disease

> **NIH VA I01** · ST. LOUIS VA MEDICAL CENTER · 2024 · —

## Abstract

Microglia are long-lived, self-replicating, yolk sac-derived immune cells of the central nervous system (CNS)
parenchyma that are critical modulators of immunity and neuropathology. Microglia dysfunction contributes to
several neurologic diseases relevant to the VA, including multiple sclerosis (MS) and amyotrophic lateral
sclerosis (ALS). In our preliminary studies, we have unexpectedly identified microglia circulating with the
cerebrospinal fluid (CSF) of patients with MS and ALS. We hypothesize that CSF microglia are endogenous
CNS cells that exhibit signatures unique to neurologic disease states. We aim to identify any disease-
associated characteristics of CSF microglia. We will explore the number and immunologic features of CSF
microglia in MS and ALS by flow cytometric analysis. To explore the molecular signature of CSF microglia in
various disease states, we will perform single cell RNA sequencing on sorted cells. Comparisons will be made
between gene expression patterns in CSF microglia between MS and ALS and in relation to healthy control
subjects to determine the health- and disease-specific profile of these cells. Finally, we will pursue flow
cytometric and RNA sequencing studies in rats, with a particular focus on models of MS and ALS, to uncover
the origins and function of CSF microglia. This proposal will lay the groundwork for the characterization of a
novel cellular population capable of regulating CNS immunity.

## Key facts

- **NIH application ID:** 10937998
- **Project number:** 5I01CX002383-03
- **Recipient organization:** ST. LOUIS VA MEDICAL CENTER
- **Principal Investigator:** Gregory Wu
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2022-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10937998

## Citation

> US National Institutes of Health, RePORTER application 10937998, Role of CSF microglia in health and disease (5I01CX002383-03). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10937998. Licensed CC0.

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