Molecular subtypes of ALS are associated with differences in patient prognosis

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease with poorly understood clinical heterogeneity, underscored by significant differences in patient age at onset, symptom progression, therapeutic response, disease duration, and comorbidity presentation. We perform a patient stratification analysis to better understand the variability in ALS pathology, utilizing postmortem frontal and motor cortex transcriptomes derived from 208 patients. Building on the emerging role of transposable element (TE) expression in ALS, we consider locus-specific TEs as distinct molecular features during stratification. Here, we identify three unique molecular subtypes in this ALS cohort, with significant differences in patient survival. These results suggest independent disease mechanisms drive some of the clinical heterogeneity in ALS.

Automated summary

In this study, the postmortem transcriptomes of 208 ALS patients were analyzed to investigate the heterogeneity of ALS pathology. Three distinct molecular subtypes were identified, which showed significant differences in patient survival. These findings suggest the existence of independent disease mechanisms driving the clinical heterogeneity in ALS.