Molecular subtypes of ALS are associated with differences in patient prognosis

Authors

Jarrett Eshima, School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ, 85287, USA.
Samantha A. O'Connor, School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ, 85287, USA.
Ethan Marschall, School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ, 85287, USA.

Document Type

Article

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.

Medical Subject Headings

Humans; Amyotrophic Lateral Sclerosis (pathology); Neurodegenerative Diseases (pathology); Comorbidity; Motor Cortex (pathology); Biological Variation, Population

Publication Date

1-6-2023

Publication Title

Nature communications

E-ISSN

2041-1723

Volume

14

Issue

1

First Page

95

PubMed ID

36609402

Digital Object Identifier (DOI)

10.1038/s41467-022-35494-w

Recommended Citation

Eshima, Jarrett; O'Connor, Samantha A.; and Marschall, Ethan, "Molecular subtypes of ALS are associated with differences in patient prognosis" (2023). Translational Neuroscience. 2302.
https://scholar.barrowneuro.org/neurobiology/2302