Journal Article

DZNE-2026-00768

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Multiplex Panel Detects Glial and Inflammatory Biomarker Signatures in Sporadic and C9orf72-ALS.

Baskar, K. ; Steffke, C. ; Bernsen, S.Extern* ; Elmas, Z. ; Hesebeck-Brinckmann, J. ; Schuster, J.DZNE* ; Meyer, T. ; Weydt, P.DZNE* ; Weishaupt, J. H.DZNE* ; Brenner, D.DZNE* ; Catanese, A. (Last author)DZNE*

2026
Wolters Kluwer Philadelphia, Pa.

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Please use a persistent id in citations: doi:10.1212/NXI.0000000000200618

Abstract: CSF proteomics has emerged as a valuable strategy for identifying diagnostic and prognostic biomarkers in amyotrophic lateral sclerosis (ALS). However, the limited availability and volumes of CSF samples restrict the broader clinical application of CSF-based biomarker panels. To address this challenge, we investigated whether the novel nucleic acid-linked immuno-sandwich assay (NULISA) multiplex platform-capable of quantifying multiple neural, glial, and inflammatory markers from minimal biofluid volumes-could validate previously proposed biomarkers and identify additional candidates relevant to ALS.Using this platform, we measured a targeted panel of 131 biomarkers in cohorts of patients with C9orf72-associated ALS, sporadic ALS (sALS), and matched healthy controls.The 6 markers neurofilament heavy chain (NEFH) and neurofilament light chain (NEFL), chitinases-particularly chitotriosidase-1 (CHIT1) and chitinase-3-like protein-1 (CHI3L1), and chemokines CCL2 and CCL3 were significantly elevated in both ALS groups compared with controls. These biomarkers correlated with disease progression and demonstrated strong diagnostic performance when combined into aggregate scores, as reflected by a high area under the receiver operating characteristic curve for ALS. Notably, C9orf72-ALS patients exhibited higher levels of the oxidative stress-related markers PRDX6 and ENO2, compared with sALS patients, suggesting a genotype-specific molecular signature.Overall, our findings support the use of a multiplexed panel of diverse, inflammatory, glial, and neurodegeneration-associated biomarkers as a complementary diagnostic and prognostic tool alongside established measurements of neurofilaments. This approach may enhance biomarker robustness while minimizing CSF volume requirements, thereby improving clinical feasibility in ALS research and care.

Keyword(s): Humans (MeSH) ; Amyotrophic Lateral Sclerosis: cerebrospinal fluid (MeSH) ; Amyotrophic Lateral Sclerosis: diagnosis (MeSH) ; Amyotrophic Lateral Sclerosis: genetics (MeSH) ; Biomarkers: cerebrospinal fluid (MeSH) ; Female (MeSH) ; Male (MeSH) ; C9orf72 Protein: genetics (MeSH) ; Middle Aged (MeSH) ; Aged (MeSH) ; Neuroglia (MeSH) ; Neuroinflammatory Diseases: cerebrospinal fluid (MeSH) ; Neurofilament Proteins: cerebrospinal fluid (MeSH) ; Adult (MeSH) ; Inflammation: cerebrospinal fluid (MeSH) ; Chitinase-3-Like Protein 1: cerebrospinal fluid (MeSH) ; Biomarkers ; C9orf72 Protein ; C9orf72 protein, human ; Neurofilament Proteins ; Chitinase-3-Like Protein 1

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Contributing Institute(s):

1. Translational Protein Biochemistry (AG Böckers)
2. Clinical Study Center (Ulm) (Clinical Study Center (Ulm))
3. Clinical Research Coordination (Clinical Research (Bonn))

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)
2. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

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Database coverage:
; ; Article Processing Charges ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; DOAJ Seal ; Essential Science Indicators ; Fees ; IF >= 5 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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