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Microglia and Immune cells interactions in multiple sclerosis cognitive impairment: a postmortem study.

Catarina Barros¹, Ainhoa Alberro², Adelaide Fernandes^3,4

¹Research Institute for Medicines (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Lisboa, Portugal.

Journal of Neuroinflammation

|December 31, 2024

Summary

Cognitive impairment in Multiple Sclerosis (MS) is linked to microglia excessively engulfing synapses, particularly inhibitory ones tagged with C1q. This process may be driven by CD8+ T cells, highlighting immune cell roles in MS cognitive deficits.

Keywords:

CD8 T cells Cognitive impairment Microglia Multiple sclerosis Synaptic pruning

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Area of Science:

Neuroscience
Immunology
Pathology

Background:

Multiple Sclerosis (MS) is a neuroinflammatory disease causing significant disability and cognitive impairment in over 50% of patients.
Understanding the mechanisms of cognitive decline in MS is crucial for developing therapeutic strategies.

Purpose of the Study:

To investigate if microglia-driven synaptic elimination and immune interactions are heightened in MS patients with cognitive impairment.
To compare these mechanisms between cognitively impaired MS patients, cognitively preserved MS patients, and non-demented controls.

Main Methods:

Postmortem hippocampal samples from non-demented controls (NDC) and MS patients were analyzed.
MS patients were categorized into cognitively preserved (MSCP) and impaired (MSCI) groups.
Immunohistochemistry was used to assess microglia density, synaptic engulfment, and CD8+ T cell interactions.

Main Results:

MSCI patients showed increased microglia actively engulfing excitatory and inhibitory synapses in the hippocampus.
A higher expression of complement protein C1q was observed at inhibitory synapses within microglia in MSCI patients.
Significant infiltration of microglia and CD8+ T cells was found in hippocampal lesions of MSCI patients.

Conclusions:

Cognitive deficits in MS are associated with microglia engulfing C1q-tagged inhibitory synapses.
CD8+ T cells may play a role in stimulating this microglia activity, contributing to cognitive deterioration in MS.