# The meninges as a neuroimmune interface: structure, barriers and roles in CNS disease

**Authors:** Sarah Joost, Hannes Kaddatz, Elise Vankriekelsvenne, Lars-Ove Brandenburg

PMC · DOI: 10.1186/s12987-026-00795-5 · Fluids and Barriers of the CNS · 2026-03-17

## TL;DR

The meninges act as a complex immune barrier for the brain, influencing diseases like Alzheimer's and multiple sclerosis.

## Contribution

This review highlights the meninges as an active neuroimmune organ with roles in disease progression and potential therapeutic targets.

## Key findings

- Meningeal layers have distinct structural and immunological roles in CNS homeostasis.
- Meningeal dysfunction contributes to diseases like bacterial meningitis and Alzheimer’s.
- The meninges influence inflammation and solute clearance in neurological disorders.

## Abstract

The meninges form a highly specialized barrier and immune interface that protects the central nervous system (CNS), regulates cerebrospinal fluid (CSF) dynamics, and coordinates communication between the CNS and the periphery. Each layer—dura mater, arachnoid mater and pia mater—possesses distinct structural, vascular and immunological features that collectively shape CNS homeostasis. A broad range of anatomical and molecular studies has revealed that meningeal compartments are far more heterogeneous and functionally complex than traditionally recognized, particularly with respect to their barrier architecture and immune interactions. In this review, we summarize current knowledge of meningeal structure and function, with a focus on barrier properties and immune-cell trafficking. We further discuss how meningeal dysfunction contributes to pathology in bacterial meningitis, multiple sclerosis and Alzheimer’s disease. Emerging evidence highlights the meninges as an active neuroimmune organ rather than a passive covering, critically influencing inflammation, solute clearance and disease progression. Understanding these mechanisms may open new therapeutic avenues targeting meningeal pathways across neurological disorders.

## Linked entities

- **Diseases:** bacterial meningitis (MONDO:0006670), multiple sclerosis (MONDO:0005301), Alzheimer’s disease (MONDO:0004975)

## Full-text entities

- **Genes:** Cd4 (CD4 antigen) [NCBI Gene 12504] {aka L3T4, Ly-4}, Pdpn (podoplanin) [NCBI Gene 14726] {aka E11, Gp38, OTS-8, RANDAM-2, T1-alpha, T1a}, CLDN5 (claudin 5) [NCBI Gene 7122] {aka AWAL, BEC1, CPETRL1, TMDVCF, TMVCF}, AQP4 (aquaporin 4) [NCBI Gene 361] {aka MIWC, MLC4, WCH4, hAQP4}, APP (amyloid beta precursor protein) [NCBI Gene 351] {aka AAA, ABETA, ABPP, AD1, APPI, CTFgamma}, PECAM1 (platelet and endothelial cell adhesion molecule 1) [NCBI Gene 5175] {aka CD31, CD31/EndoCAM, GPIIA', PECA1, PECAM-1, endoCAM}, Pecam1 (platelet/endothelial cell adhesion molecule 1) [NCBI Gene 18613] {aka Cd31, PECAM-1, Pecam}, Lyve1 (lymphatic vessel endothelial hyaluronan receptor 1) [NCBI Gene 114332] {aka 1200012G08Rik, Crsbp-1, Lyve-1, Xlkd1}, Prox1 (prospero homeobox 1) [NCBI Gene 19130] {aka A230003G05Rik, PROX-1}, CSF2 (colony stimulating factor 2) [NCBI Gene 1437] {aka CSF, GMCSF}
- **Diseases:** dementia (MESH:D003704), autoimmune (MESH:D001327), vascular dysfunction (MESH:D002561), meningioma (MESH:D008579), Bacterial meningitis (MESH:D016920), Bacterial and viral infections (MESH:D014777), malignancies (MESH:D009369), MS (MESH:D009103), tension-type headaches (MESH:D018781), migraines (MESH:D008881), secondary headaches (MESH:D051271), impairment of neurological function (MESH:D003291), obstructive hydrocephalus (MESH:D006849), visual disturbances (MESH:D014786), meningeal dysfunction (MESH:D008580), AD (MESH:D000544), fever (MESH:D005334), amyloid (MESH:C000718787), neurological disorders (MESH:D009461), Meningeal inflammation (MESH:D007249), amyloid angiopathy (MESH:C538248), motor and sensory deficits (MESH:D001289), primary headaches (MESH:D051270), cerebral amyloid angiopathy (MESH:D016657), traumatic brain injury (MESH:D000070642), impairment of consciousness (MESH:D003244), axonal degeneration (MESH:D009410), infection (MESH:D007239), hemorrhages (MESH:D006470), injury (MESH:D014947), subarachnoid hemorrhage (MESH:D013345), stroke (MESH:D020521), vascular injury (MESH:D057772), cortical demyelination (MESH:D003711), EAE (MESH:D004681), neuroinflammation (MESH:D000090862), neurotoxic (MESH:D020258), cognitive impairment (MESH:D003072), cortical lesions (MESH:D054220), hematoma (MESH:D006406), pneumococcal meningitis (MESH:D008586), neurodegeneration (MESH:D019636), CNS disease (MESH:D002493), bacteraemia (MESH:C531821), neurological disease (MESH:D020271), neurological sequelae (MESH:D009422), headache (MESH:D006261), neck stiffness (MESH:D006258)
- **Chemicals:** hematoxylin (MESH:D006416), glucose (MESH:D005947), water (MESH:D014867), azan (-), eosin (MESH:D004801)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116], Streptococcus pneumoniae (species) [taxon 1313], Mus musculus (house mouse, species) [taxon 10090], Bacteria Latreille et al. 1825 (Bacteria stick insect, genus) [taxon 629395], Neisseria meningitidis (species) [taxon 487], Homo sapiens (human, species) [taxon 9606], Ovis aries (domestic sheep, species) [taxon 9940]

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12998060/full.md

## References

2 references — full list in the complete paper: https://tomesphere.com/paper/PMC12998060/full.md

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Source: https://tomesphere.com/paper/PMC12998060