Molecular subgroups of ALS patients with distinct survival outcomes identified through plasma proteomics

Abstract

Amyotrophic Lateral Sclerosis (ALS) is a phenotypically diverse neurodegenerative disorder characterized by the degeneration of motor neurons, ultimately resulting in loss of motor function. Currently, patients are classified based on clinical factors which does not fully capture the heterogeneity. Using the Olink Explore HT, we profiled [~]5400 plasma proteins in ALS patients (n = 235) from the ALSrisc Study at Karolinska Institutet, Sweden, and applied consensus clustering, which revealed three patient subgroups significantly differing in survival outcome. Weighted gene correlation network analysis (WGCNA) and gene ontology (GO) analysis identified protein modules related to biological functions including cellular stress response and Rho-GTPase activity for the shorter surviving patient group. Cell-type enrichment analysis indicating a broad cellular origin of the circulating proteome, with contributions from nervous system cells, vascular cells, immune cells, and muscle cells. Our work highlights the potential of plasma proteomics for clinically meaningful patient stratification in ALS.

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BibTeX RIS

BibTeX

@misc{aksoylu2026molecular,
  title = {{Molecular subgroups of ALS patients with distinct survival outcomes identified through plasma proteomics}},
  author = {I. S. Aksoylu and L. Azizi and L. Öijerstedt and S. Lilja and M. B. Alvez and S. Yazdani and L. Skoglund and J. Foucher and A. Juto and C. Seitz and R. Press and K. Samuelsson and U. Kläppe and F. Fang and M. Uhlen and F. Edfors and P. Nilsson and C. Ingre and A. Manberg},
  howpublished = {medRxiv},
  year = {2026},
  month = sep,
  doi = {10.64898/2026.09.16.26362998},
  url = {https://www.medrxiv.org/content/10.64898/2026.09.16.26362998v1},
  note = {CC BY-NC-ND},
}

RIS

TY  - UNPB
TI  - Molecular subgroups of ALS patients with distinct survival outcomes identified through plasma proteomics
AU  - I. S. Aksoylu
AU  - L. Azizi
AU  - L. Öijerstedt
AU  - S. Lilja
AU  - M. B. Alvez
AU  - S. Yazdani
AU  - L. Skoglund
AU  - J. Foucher
AU  - A. Juto
AU  - C. Seitz
AU  - R. Press
AU  - K. Samuelsson
AU  - U. Kläppe
AU  - F. Fang
AU  - M. Uhlen
AU  - F. Edfors
AU  - P. Nilsson
AU  - C. Ingre
AU  - A. Manberg
PY  - 2026
DA  - 2026/09/16
PB  - medRxiv
DO  - 10.64898/2026.09.16.26362998
UR  - https://www.medrxiv.org/content/10.64898/2026.09.16.26362998v1
AB  - Amyotrophic Lateral Sclerosis (ALS) is a phenotypically diverse neurodegenerative disorder characterized by the degeneration of motor neurons, ultimately resulting in loss of motor function. Currently, patients are classified based on clinical factors which does not fully capture the heterogeneity. Using the Olink Explore HT, we profiled [~]5400 plasma proteins in ALS patients (n = 235) from the ALSrisc Study at Karolinska Institutet, Sweden, and applied consensus clustering, which revealed three patient subgroups significantly differing in survival outcome. Weighted gene correlation network analysis (WGCNA) and gene ontology (GO) analysis identified protein modules related to biological functions including cellular stress response and Rho-GTPase activity for the shorter surviving patient group. Cell-type enrichment analysis indicating a broad cellular origin of the circulating proteome, with contributions from nervous system cells, vascular cells, immune cells, and muscle cells. Our work highlights the potential of plasma proteomics for clinically meaningful patient stratification in ALS.
ER  -

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