TY - JOUR
T1 - Molecular subtypes of ALS are associated with differences in patient prognosis
AU - NYGC ALS Consortium
AU - Eshima, Jarrett
AU - O’Connor, Samantha A.
AU - Marschall, Ethan
AU - Bowser, Robert
AU - Plaisier, Christopher L.
AU - Smith, Barbara S.
N1 - Publisher Copyright:
© 2023, The Author(s).
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85145870335&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85145870335&partnerID=8YFLogxK
U2 - 10.1038/s41467-022-35494-w
DO - 10.1038/s41467-022-35494-w
M3 - Article
C2 - 36609402
AN - SCOPUS:85145870335
SN - 2041-1723
VL - 14
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 95
ER -