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Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
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Comprehensive Autopsy Program for Individuals with Multiple Sclerosis

Published on: July 19, 2019

Microglial states associate with lesion dynamics in multiple sclerosis

Aletta M R van den Bosch1, Jia Hui Khoo2, Zhigang Lu2

  • 1Neuroimmunology Research Group, Netherlands Institute for Neuroscience, Amsterdam, the Netherlands.

Cell Reports
|June 10, 2026
PubMed

Insights

Microglia in multiple sclerosis (MS) lesions show distinct states. Foamy microglia are linked to immune activation and lesion expansion, while ramified microglia associate with myelin repair and axonal support.

Area of Science:

  • Neuroscience
  • Immunology
  • Pathology

Background:

  • Multiple sclerosis (MS) is a central nervous system (CNS) neuroinflammatory disease.
  • Lesion expansion in MS correlates with disability progression, while remyelination offers potential for functional recovery.
  • The precise role of microglial states in these divergent outcomes is not fully understood.

Purpose of the Study:

  • To investigate the distinct cellular and molecular characteristics of microglial states within MS lesions.
  • To understand the spatial relationship between microglial morphology and lesion pathology or repair.

Main Methods:

  • Utilized single-cell-resolution spatial transcriptomics on postmortem human brain tissue.
  • Compared gene expression profiles and cellular signatures in MS lesions with foamy versus ramified microglia.

Main Results:

  • Identified distinct molecular and cellular signatures spatially associated with microglial morphology.
  • Lesions with ramified microglia showed gene expression linked to myelin stability and axonal support, suggesting a repair-permissive environment.
  • Lesions with foamy microglia exhibited immune activation, immunoglobulin production, complement activity, iron dysregulation, and demyelination, indicating active pathology.

Conclusions:

  • Microglial states within MS lesions are spatially segregated and associated with distinct molecular programs.
  • Foamy microglia are linked to lesion expansion and pathology, whereas ramified microglia are associated with repair.
  • These findings reveal distinct immune-glial niches influencing disease progression and repair in multiple sclerosis.
Keywords:
CP: immunologyCP: neurosciencelesion expansionmicroglia statemultiple sclerosisremyelinationspatial transcriptomics

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