articleNature ImmunologyJan 27, 2026HYBRID OA

Clonal CD8+ T cells populate the leptomeninges and coordinate with immune cells in human degenerative brain diseases

RHRyan HobsonSHSamuel H. S. LevyCMChitra Mohinder Singh SingalDFDelaney FlahertyHXHarrison Xiao

Columbia University Irving Medical Center · Standard Bio (Norway) · +1 more institution

PubMed
Indexed incrossrefpubmed

Abstract

Meningeal immune cells monitor the central nervous system (CNS) and influence neuroinflammation in mice, but the human leptomeningeal immune landscape and the changes that occur in this immunological niche in neurodegeneration remain underexplored. Here we performed single-cell RNA and T cell receptor (TCR) sequencing of 99,625 high-quality immune cells from 57 leptomeninges and brain samples from donors with Alzheimer’s disease (AD), amyotrophic lateral sclerosis and Parkinson’s disease and found that although the leptomeninges are home to highly clonally expanded CD8 tissue-resident memory (TRM) T cells, the maximal level of clonal expansion was decreased in AD in comparison to non-neurodegenerative…

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6
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86.29
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100%
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13

Topics & keywords

Topics
Keywords
  • Leptomeninges
  • Immune system
  • Neuroinflammation
  • CD8
  • Neurodegeneration
  • Microglia
  • Human brain
  • T-cell receptor
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