Molecular Subtypes of Amyotrophic Lateral Sclerosis: A Gene Expression Analysis

Abstract

Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive paralysis, with most patients surviving only 2-5 years after diagnosis. While the exact cause is unknown, TDP-43 protein dysfunction and sporadic gene mutations are common. Recently, researchers have categorized ALS into three distinct molecular subtypes: ALS-Glia (microglial activation and neuroinflammation), ALS-TE (TDP-43 pathology and transposable element silencing), and ALS-Ox (mitochondrial stress and oxidative phosphorylation). Using a dataset of post-mortem samples of control and ALS patients from the NYGC ALS Consortium, this study analyzed gene expression across these three subtypes. We identified subtype-specific genes linked to metabolic and immune pathways using differential expression and biological pathway analysis. These insights contribute to a deeper understanding of the molecular basis of ALS and can ultimately inform the development of more targeted, individualized therapeutic approaches.