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Exploring the Disease-Associated Microglia State in Amyotrophic Lateral Sclerosis

Carlota Jauregui1, Idoia Blanco-Luquin2, Mónica Macías2

  • 1Neurology Department, Hospital Universitario de Navarra (HUN), IdiSNA (Navarra Institute of Health Research), 31008 Pamplona, Spain.

Biomedicines
|November 25, 2023
PubMed
Abstract

Insights

Disease-associated microglia (DAM) show an inflammatory response in amyotrophic lateral sclerosis (ALS). Key genes like TREM2, CD33, and MS4A are elevated, suggesting their role in ALS pathology and potential as therapeutic targets.

Area of Science:

  • Neuroscience
  • Immunology
  • Genetics

Background:

  • Neuroinflammation, particularly involving microglia, is implicated in amyotrophic lateral sclerosis (ALS) pathophysiology.
  • Disease-associated microglia (DAM) represent a distinct microglial state observed in neurodegenerative diseases.
  • Understanding microglial gene expression in ALS is crucial for identifying therapeutic targets.

Purpose of the Study:

  • To investigate the expression patterns of microglial-related genes in the spinal cord of ALS patients.
  • To compare gene expression profiles between homeostatic and disease-associated microglia in ALS.
  • To identify specific genes involved in the microglial response during ALS progression.

Main Methods:

  • Analysis of mRNA expression levels using RT-qPCR.
  • Examination of postmortem spinal cord tissue from ALS and control donors.
  • Quantification of genes associated with microglial homeostatic and DAM states.

Main Results:

  • Elevated expression of TREM2, MS4A, CD33, APOE, and TYROBP in ALS spinal cord tissue compared to controls (p < 0.05).
  • No significant differences in TMEM119, SPP1, and LPL gene expression were observed between ALS and control groups.
  • These findings indicate specific microglial gene dysregulation in ALS.

Conclusions:

  • A DAM-mediated inflammatory response is suggested to be present in ALS.
  • TREM2 plays a significant role in microglial immune function within the context of ALS.
  • CD33 and MS4A are supported as genes involved in the physiopathology of ALS, highlighting their potential as therapeutic targets.
Keywords:
CD33MS4Aamyotrophic lateral sclerosisdisease-associated microglianeurodegenerationneuroinflammation

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