Blood-based biomarker discovery in motor neuron disease using nucleic acid-linked immuno-sandwich assay

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ID: 314986
2026
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Abstract
Abstract Motor Neuron Disease (MND) presents with phenotypic heterogeneity, is diagnostically challenging, and has poor prognosis. The absence of accessible blood-based biomarkers has hampered progress towards precision medicine. Highly sensitive immunoassays offer considerable promise for identifying blood-based biomarkers informing underlying pathophysiology and enabling accurate diagnosis and monitoring. We report findings on parallel use of the ultra-sensitive multiplexed NUcleic Acid-Linked Immuno-Sandwich Assay (NULISA) and Single molecule array (Simoa), to interrogate serum from people with MND. Sera (48 MND, 38 controls) were analysed using a NULISAseq targeted neurodegenerative panel and a Simoa Neurofilament light chain (NfL) and glial fibrillary acid protein (GFAP) duplex assay. Neurofilament light and heavy chain, total tau (t-tau), phosphorylated tau (pTau) - 181, pTau-217, pTau-231, fatty acid binding protein 3 (FABP3), amyloid beta (Aβ) 38 and Aβ40 levels were significantly elevated in MND (p < 0.05). Simoa and NULISAseq assays demonstrated strong correlations for NfL and GFAP (r > 0.90). Use of the multiplexed NULISAseq panel confirmed a well-established NfL elevation in MND, and replicated findings for other proteins from recent studies. Results add confidence in the validity and reproducibility of biomarkers identified using NULISAseq, while offering insights into the underlying pathophysiology and heterogeneity of MND.
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Authors Hatice Bozkurt, Katy R. Reid, Judith Newton, Jessica Gill, Isaac Chau, Chloe Parker, Hatice Kurucu King, Johnny Tam, Dominic Ng, Maria Stavrou, Paul Baxter, Orla Marland, Karen Burr, Amanda Heslegrave, Elena Veleva, Owen Swann, Henrik Zetterberg, David Hunt, Bhuvaneish T. Selvaraj, Siddharthan Chandran, Suvankar Pal
Journal Brain communications
Year 2026
DOI
10.1093/braincomms/fcag180
URL
https://doi.org/10.1093/braincomms/fcag180
Keywords Keywords not found

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