# Single-cell elderly blood–CSF atlas implicates peripherally influenced immune dysregulation in normal pressure hydrocephalus

**Authors:** Phan Q. Duy, Emre Kiziltug, Ana B.W. Greenberg, Neel H. Mehta, Le T. Hao, Carla Fortes, Susan Mullany, Baojian Fan, Ani Manichaikul, Andrew F. Teich, Diane Chan, Seth L. Alper, Bradley T. Hyman, Steven E. Arnold, Guy M. McKhann, Matthew P. Frosch, Kristopher T. Kahle

PMC · DOI: 10.1073/pnas.2412159122 · 2025-05-05

## TL;DR

This study uses single-cell RNA sequencing to explore immune changes in blood and spinal fluid of patients with normal pressure hydrocephalus.

## Contribution

The study provides a detailed single-cell atlas linking peripheral immune changes to central nervous system alterations in iNPH.

## Key findings

- Proinflammatory monocytes in blood and CSF are associated with lower cognitive function in iNPH patients.
- CSF contains cell populations likely from degenerating brain cells near the ventricles.
- Findings suggest immune dysregulation in blood and CSF of iNPH patients.

## Abstract

We have generated a single-cell RNA sequencing atlas of peripheral blood and ventricular CSF in idiopathic normal pressure hydrocephalus (iNPH) patients totaling 140,207 single-cell transcriptomes. We found proinflammatory alterations in peripheral blood and CSF monocytes in iNPH patients with lower baseline cognitive function. We also identified CSF cell populations likely representing periventricular sloughing of degenerating neuroglial cells. Our findings suggest possible immune dysregulation in the blood and CSF of iNPH patients.

## Linked entities

- **Diseases:** normal pressure hydrocephalus (MONDO:0009366)

## Full-text entities

- **Genes:** CSF2 (colony stimulating factor 2) [NCBI Gene 1437] {aka CSF, GMCSF}
- **Diseases:** immune (MESH:D007154), iNPH (MESH:D006850), hydrocephalus (MESH:D006849)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

1 figure with captions in the complete paper: https://tomesphere.com/paper/PMC12087963/full.md

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Source: https://tomesphere.com/paper/PMC12087963