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Neurodegenerative disorders are progressive diseases that cause irreversible damage and loss to neurons in specific brain areas. Examples of these disorders include Parkinson's disease, Alzheimer's disease, Multiple Sclerosis (MS), and Amyotrophic Lateral Sclerosis (ALS). These disorders share characteristics such as proteinopathies, selective neuronal vulnerability, and a complex interplay between genetic and environmental factors. The primary therapeutic goal for these conditions is...
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Related Experiment Video

Updated: Aug 13, 2025

Real-Time Fluorescent Measurement of Synaptic Functions in Models of Amyotrophic Lateral Sclerosis
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Profiling TREM2 expression in amyotrophic lateral sclerosis.

Ivonne Jericó1, Janire Vicuña-Urriza2, Idoia Blanco-Luquin2

  • 1Department of Neurology, University Hospital of Navarra-IdisNA (Navarra Institute of Health Research), Pamplona, Spain; Neuromuscular and Neuron Motor Neuron Diseases Laboratory, IdisNA (Navarra Institute of Health Research), Pamplona, Spain.

Brain, Behavior, and Immunity
|January 21, 2023
PubMed
Summary

Soluble TREM2 (sTREM2) levels are elevated in cerebrospinal fluid and blood of amyotrophic lateral sclerosis (ALS) patients, suggesting its role in ALS pathogenesis and potential as a non-invasive biomarker. Phosphorylated TDP-43 in CSF also predicts ALS.

Keywords:
Amyotrophic lateral sclerosisBiomarkerMicrogliaNeuroinflammationPeripheral inflammationSerum and CSFSoluble TREM2TDP-43TREM2TREM2 isoforms

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Area of Science:

  • Neuroscience
  • Immunology
  • Genetics

Background:

  • Neuroinflammation, particularly involving microglia, is implicated in amyotrophic lateral sclerosis (ALS) pathogenesis.
  • The TREM2 gene is critical for microglial function in neurodegenerative diseases.

Purpose of the Study:

  • To investigate TREM2 expression in ALS and evaluate soluble TREM2 (sTREM2) as a potential biomarker.
  • To assess if combined sTREM2 measurements improve diagnostic yield with TDP-43 levels.

Main Methods:

  • Case-control study analyzing TREM2 mRNA and protein in postmortem spinal cords.
  • ELISA measured sTREM2, total TDP-43 (tTDP-43), and phosphorylated TDP-43 (pTDP-43) in CSF and serum.
  • Logistic regression analyzed associations with ALS status.

Main Results:

  • TREM2 mRNA and protein were upregulated in ALS spinal cords.
  • Significantly higher sTREM2 levels were found in CSF and serum of ALS patients.
  • Both CSF and serum sTREM2 were independently associated with ALS status.
  • pTDP-43 in CSF independently predicted ALS.

Conclusions:

  • TREM2 is deregulated in ALS, supporting its role in the disease.
  • sTREM2 in CSF and blood are potential non-invasive biomarkers for ALS.
  • pTDP-43 in CSF may serve as an ALS biomarker.