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Brain communications
Published

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

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 J Swann, Henrik Zetterberg, David P J Hunt, Bhuvaneish Thangaraj Selvaraj, Siddharthan Chandran, Suvankar Pal

Abstract

Brain Commun. 2026 May 26;8(3):fcag180. doi: 10.1093/braincomms/fcag180. eCollection 2026.

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, 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.

PMID:42375130 | PMC:PMC13312953 | DOI:10.1093/braincomms/fcag180

UK DRI Authors

Dr Amanda Heslegrave

Principal Research Fellow

Co-leading the UK DRI Biomarker Factory platform based at UK DRI at UCL

Dr Amanda Heslegrave

Elena Veleva

UK DRI Facility Co-ordinator

Facility Co-ordinator, UK DRI Biomarker Factory

Elena Veleva

Prof Henrik Zetterberg

Group Leader

Pioneering the development of fluid biomarkers for dementia

Prof Henrik Zetterberg

Prof Siddharthan Chandran

Director & CEO

Dissecting a genetic cause of ALS and FTD and identifying ways to help protect neurons

Prof Siddharthan Chandran

Prof Suvankar Pal

Group Leader

Clinically active academic neurologist specialising in motor neuron disease

Prof Suvankar Pal