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 stratifica...

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Bibliographic Details
Published in:Nature communications 2023-01, Vol.14 (1), p.95-95, Article 95
Main Authors: Eshima, Jarrett, O’Connor, Samantha A., Marschall, Ethan, Bowser, Robert, Plaisier, Christopher L., Smith, Barbara S.
Format: Article
Language:English
Subjects:
38/91
631/337/2019
631/378/1689/1285
631/378/340
Amyotrophic lateral sclerosis
Amyotrophic Lateral Sclerosis - pathology
Biological Variation, Population
Biomarkers
Comorbidity
Cortex (frontal)
Cortex (motor)
Gene expression
Heterogeneity
Humanities and Social Sciences
Humans
Independent sample
Medical prognosis
Motor Cortex - pathology
multidisciplinary
Neurodegeneration
Neurodegenerative diseases
Neurodegenerative Diseases - pathology
Neurosciences
Oxidative stress
Pathology
Patients
Principal components analysis
Science
Science (multidisciplinary)
Survival
Transcriptomes
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Summary: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. Variability in ALS disease onset and progression are poorly understood. Our work identifies three distinct molecular states in post-mortem tissue that capture some of the observed differences in patient age of onset and survival.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-022-35494-w