Characterizing ALS Subtypes in the Choroid Plexus and their Role in Patient Prognosis

Abstract

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disorder that primarily affects motor neurons, leading to muscle weakness, paralysis, and ultimately, respiratory failure or death. Through the application of unsupervised clustering techniques, we identified three distinct ALS subgroups based on gene expression profiles and transposable element activity in the choroid plexus. Gene set enrichment analysis revealed subtype-specific biological pathways, including immune signaling in ALS-Glia, mitochondrial dysfunction in ALS-Ox, and retrotransposon activity in ALS-TD. Survival analysis highlighted significant differences in disease progression among the subtypes, with ALS-Ox patients exhibiting the longest survival. These findings offer valuable insights into the molecular mechanisms underlying ALS in the choroid plexus and their potential impact on clinical outcomes, providing a foundation for the development of personalized therapeutic approaches.

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