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Updated: May 15, 2026
Analysis of Microglia and Monocyte-derived Macrophages from the Central Nervous System by Flow Cytometry
Published on: June 22, 2017
A CSF disease-associated macrophage signature defines progressive multiple sclerosis
Anna-Lena Börsch1, Frederike Riethues1, Andreas Schulte-Mecklenbeck1
1Department of Neurology, Medical Faculty, University Hospital Münster, Münster, Germany.
Objective:
Progression in multiple sclerosis (MS) often corresponds to irreversible disability in MS patients. Cellular changes in the cerebrospinal fluid (CSF) have provided biomarkers and mechanisms in relapsing-remitting MS (RRMS) but remain understudied in primary and secondary progressive MS (summarized herein as PMS).
Methods:
We combined retrospective flow cytometry of CSF cells from RRMS (n = 169), PMS (n = 56), and non-inflammatory controls (n = 74) with prospective CSF single-cell transcriptomics of 35 individuals (11 controls, 12 RRMS, and 12 PMS) and with confirmatory CSF ELISA. Available CSF single-cell data from age-matched and Alzheimer's disease (AD) patients served as additional controls.
Results:
Proportions of CD14+ monocytes in CSF are increased in PMS and correlated with clinical surrogate markers of progression. Transcriptionally, these monocytes resembled border-associated macrophages (BAM)-like cells with a chronically activated antigen-presenting phenotype. Additionally, these monocytes shared some features with disease-associated microglia/macrophages (DAM), previously identified in neurodegeneration. Induction of DAM-associated molecules, including transcribed and soluble TREM2 (sTREM2), characterized secondary progressive MS (SPMS) and supported its differential diagnosis.
Interpretation:
We thus identified MS stage-specific CSF signatures and shared cellular features of degeneration detectable in CSF of PMS patients.
Insights
Cellular changes in cerebrospinal fluid (CSF) reveal distinct signatures in progressive multiple sclerosis (PMS). Increased monocytes in PMS CSF resemble activated macrophages, offering potential biomarkers for disease progression.
Area of Science:
- Neuroimmunology
- Cellular Biology
- Biomarker Discovery
Background:
- Multiple sclerosis (MS) progression leads to irreversible disability.
- Cerebrospinal fluid (CSF) cellular changes are known biomarkers in relapsing-remitting MS (RRMS).
- Cellular changes in progressive MS (PMS) remain understudied.
Purpose of the Study:
- To investigate CSF cellular and molecular signatures in primary and secondary progressive MS (PMS).
- To identify potential biomarkers for MS progression and differential diagnosis.
Main Methods:
- Retrospective flow cytometry of CSF cells from RRMS, PMS, and controls.
- Prospective CSF single-cell transcriptomics.
- Confirmatory CSF ELISA and analysis of age-matched/Alzheimer's disease patient data.
Main Results:
- CSF CD14+ monocytes are increased in PMS and correlate with progression markers.
- These monocytes exhibit a chronically activated, antigen-presenting phenotype, resembling border-associated macrophages (BAMs).
- Monocytes share features with disease-associated microglia/macrophages (DAMs); TREM2 induction is noted in secondary progressive MS (SPMS).
Conclusions:
- Identified MS stage-specific CSF signatures.
- Detected shared cellular features of degeneration in PMS patients' CSF.
- Highlighted potential of CSF monocytes and TREM2 as biomarkers for PMS and SPMS diagnosis.
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