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

P Phan Q. Duy E Emre Kiziltug (Department of Neurosurgery, Massachusetts General Hospital) A Ana B.W. Greenberg (Department of Neurosurgery, Massachusetts General Hospital) N Neel H. Mehta (Department of Neurosurgery, Massachusetts General Hospital) L Le T. Hao (Department of Neurosurgery, Yale University School of Medicine) C Carla Fortes (Department of Neurosurgery, Massachusetts General Hospital) S Susan Mullany (Department of Neurosurgery, Massachusetts General Hospital) B Baojian Fan (Department of Neurosurgery, Massachusetts General Hospital) A Ani Manichaikul (Department of Genome Sciences, Center for Public Health Genomics, University of Virginia) A Andrew F. Teich (Department of Pathology and Cell Biology, Columbia University) D Diane Chan (Department of Neurology, Massachusetts General Hospital) S Seth L. Alper (Division of Nephrology and Department of Medicine, Beth Israel Deaconess Medical Center) B Bradley T. Hyman S Steven E. Arnold (Department of Neurology, Massachusetts General Hospital) G Guy M. McKhann (Department of Neurosurgery, Columbia University) M Matthew P. Frosch (Department of Neurology, Massachusetts General Hospital) K Kristopher T. Kahle (Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School)

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.

Article Details

Volume / Issue Vol. 122, Issue 19
Published May 13, 2025
ISSN 0027-8424
Publisher National Academy of Sciences

Authors (17)

P

Phan Q. Duy

E

Emre Kiziltug

Department of Neurosurgery, Massachusetts General Hospital

A

Ana B.W. Greenberg

Department of Neurosurgery, Massachusetts General Hospital

N

Neel H. Mehta

Department of Neurosurgery, Massachusetts General Hospital

L

Le T. Hao

Department of Neurosurgery, Yale University School of Medicine

C

Carla Fortes

Department of Neurosurgery, Massachusetts General Hospital

S

Susan Mullany

Department of Neurosurgery, Massachusetts General Hospital

B

Baojian Fan

Department of Neurosurgery, Massachusetts General Hospital

A

Ani Manichaikul

Department of Genome Sciences, Center for Public Health Genomics, University of Virginia

A

Andrew F. Teich

Department of Pathology and Cell Biology, Columbia University

D

Diane Chan

Department of Neurology, Massachusetts General Hospital

S

Seth L. Alper

Division of Nephrology and Department of Medicine, Beth Israel Deaconess Medical Center

B

Bradley T. Hyman

S

Steven E. Arnold

Department of Neurology, Massachusetts General Hospital

G

Guy M. McKhann

Department of Neurosurgery, Columbia University

M

Matthew P. Frosch

Department of Neurology, Massachusetts General Hospital

K

Kristopher T. Kahle

Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School