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Molecular subtypes of ALS are associated with differences in patient prognosis

Author

Listed:
  • Jarrett Eshima

    (Arizona State University)

  • Samantha A. O’Connor

    (Arizona State University)

  • Ethan Marschall

    (Arizona State University)

  • Robert Bowser

    (Barrow Neurological Institute
    Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center)

  • Christopher L. Plaisier

    (Arizona State University)

  • Barbara S. Smith

    (Arizona State University)

Abstract

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.

Suggested Citation

  • Jarrett Eshima & Samantha A. O’Connor & Ethan Marschall & Robert Bowser & Christopher L. Plaisier & Barbara S. Smith, 2023. "Molecular subtypes of ALS are associated with differences in patient prognosis," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-022-35494-w
    DOI: 10.1038/s41467-022-35494-w
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    References listed on IDEAS

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