2026 American Academy of Neurology Abstract Website

Objective:

Identification of novel disease-associated proteins across cerebrospinal fluid (CSF) and plasma from ALS patients.

Background:

In ALS there have been limited biomarkers identified which can be used to diagnose, predict the course of, or assess treatment response for the disease.

Design/Methods:

We performed proteomic analysis using the Olink® Explore 3072 platform. Procured CSF and plasma samples from ALS patients (CSF: n = 44; plasma: n = 34) and age-matched healthy controls (CSF: n = 55; plasma: n = 30) were used for proteomic analyses. A sub-set of subjects had both CSF and plasma samples (ALS: n = 17 and controls: n = 21) allowing us to compare protein expression levels for the same donors across matrices.

Results:

In CSF, we identified previously reported proteins that are differentially expressed in ALS, including Neurofilament light (NfL) and Chitinase 1 (CHIT1). Importantly, in both matrices, we have identified several novel biomarkers associated with immune and muscle-related pathways. Gene set enrichment analysis (GSEA) of differentially expressed proteins in both CSF and plasma showed enrichment of muscle-related proteins including MYBPC1 (r=0.72), MYL3 (r=0.82) and MYOM3 (r=0.81). Furthermore, in a cross-sectional analysis, ADAMTS8 was found to be significantly associated with ALSFRS-R scores (r=0.78, FDR q < 0.5).

Conclusions:

We demonstrate that there is an overlap of the proteome across plasma and CSF associated with ALS. This may facilitate the use of plasma as a surrogate for disease processes in the CSF, a more difficult-to-obtain matrix. We also found novel muscle related proteins as potential biomarkers, which may allow further understanding of ALS pathophysiology and inform research on disease progression and treatment response.