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

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.

Fig. 1.

A single-cell multitissue atlas of human iNPH. (A) Uniform Manifold Approximation and Projection (UMAP) plot representing 13 color-coded cell clusters identified in merged single-cell transcriptomes of blood (128,027) and CSF (12,180) cells from 10 iNPH patients. Cluster names were manually assigned. (B) Dotpot depicting selected marker genes in blood and CSF cell clusters. Dot size encodes percentage of cells expressing the gene, color encodes the average per cell gene expression level. (C) UMAP plots comparing blood (Left) and CSF (Right) cell clustering. (D) Volcano plot depicting differences in cluster abundance in CSF compared to blood plotting fold change (log₂) against P value (−log₁₀) based on beta-binomial regression. Horizontal line indicates significance threshold. (E) UMAP plots comparing CSF cell clustering in iNPH patients with high MoCA scores (Left) and low MoCA scores (Right). (F) Volcano plot depicting differences in cluster abundance in the CSF of iNPH patients with high MoCA scores compared to those with low MoCA scores plotting fold change (log₂) against P value (−log₁₀) based on beta-binomial regression. Horizontal line indicates significance threshold. (G) Heatmap showing cell type–specific gene expression changes in the CSF of iNPH patients with low MoCA scores compared to those with high MoCA scores. (H–K) GO analysis (biological processes) of top marker genes for each cell cluster.