Abstract Details

Title High-throughput Proteomics in CSF and Plasma from ALS Patients Identifies Novel Biomarkers Related to Muscle Structure and Function

Topic General Neurology

Presentation(s) S32 - General Neurology 1 (4:18 PM-4:30 PM)

Poster/Presentation
Number 005

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.

Authors/Disclosures
Aparna Vasanthakumar, PhD PRESENTER	Dr. Vasanthakumar has received personal compensation for serving as an employee of Abbvie. Dr. Vasanthakumar has stock in Abbvie.
Jennifer Mollon, PhD	Dr. Mollon has received personal compensation for serving as an employee of AbbVie Deutschland GmbH & Co KG. Dr. Mollon has stock in AbbVie Inc.
Romica Kerketta, PhD	Dr. Kerketta has received personal compensation for serving as an employee of AbbVie. Dr. Kerketta has or had stock in AbbVie.
Anahita Bhathena, PhD	Dr. Bhathena has received personal compensation for serving as an employee of AbbVie. Dr. Bhathena has stock in AbbVie.
Bill Cho, MD, PhD (Calico)	Dr. Cho has received personal compensation for serving as an employee of Calico. Dr. Cho has stock in Roche.
Amos Baruch (Calico)	Dr. Baruch has received personal compensation for serving as an employee of Calico Life Science.
Nicholas Seneca	Dr. Seneca has received personal compensation for serving as an employee of Abbvie. Dr. Seneca has stock in Abbvie .

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