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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)\u2014181, pTau-217, pTau-231, fatty acid binding protein 3, amyloid beta (A\u03b2) 38 and A\u03b240 levels were significantly elevated in MND (P &amp;lt; 0.05). Simoa and NULISAseq assays demonstrated strong correlations for NfL and GFAP (r &amp;gt; 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.<\/jats:p>","DOI":"10.1093\/braincomms\/fcag180","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T07:40:41Z","timestamp":1779781241000},"source":"Crossref","is-referenced-by-count":3,"title":["Blood-based biomarker discovery in motor neuron disease using nucleic acid-linked immuno-sandwich assay"],"prefix":"10.1093","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3043-493X","authenticated-orcid":false,"given":"Hatice","family":"Bozkurt","sequence":"first","affiliation":[{"name":"Anne Rowling Regenerative Neurology Clinic, University of Edinburgh , Edinburgh, EH16 4SB ,","place":["UK"]},{"name":"Euan MacDonald Centre for Motor Neuron Disease Research, University of Edinburgh , Edinburgh, EH16 4SB ,","place":["UK"]},{"name":"Institute for Neuroscience and Cardiovascular Research, University of Edinburgh , Edinburgh, EH16 4TJ ,","place":["UK"]},{"name":"UK Dementia Research Institute, University of Edinburgh , Edinburgh, EH16 4SB ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katy R","family":"Reid","sequence":"additional","affiliation":[{"name":"Anne Rowling Regenerative Neurology Clinic, University of Edinburgh , Edinburgh, EH16 4SB ,","place":["UK"]},{"name":"Euan MacDonald Centre for Motor Neuron Disease Research, University of Edinburgh , Edinburgh, EH16 4SB ,","place":["UK"]},{"name":"Institute for Neuroscience and Cardiovascular Research, University of Edinburgh , Edinburgh, EH16 4TJ ,","place":["UK"]},{"name":"UK Dementia Research Institute, University of Edinburgh , Edinburgh, EH16 4SB ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Newton","sequence":"additional","affiliation":[{"name":"Anne Rowling Regenerative Neurology Clinic, University of Edinburgh , Edinburgh, EH16 4SB ,","place":["UK"]},{"name":"Euan MacDonald Centre for Motor Neuron Disease Research, University of Edinburgh , Edinburgh, EH16 4SB ,","place":["UK"]},{"name":"Institute for Neuroscience and Cardiovascular Research, University of Edinburgh , Edinburgh, EH16 4TJ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Gill","sequence":"additional","affiliation":[{"name":"Anne Rowling Regenerative Neurology Clinic, University of Edinburgh , Edinburgh, EH16 4SB ,","place":["UK"]},{"name":"Euan MacDonald Centre for Motor Neuron Disease Research, University of Edinburgh , Edinburgh, EH16 4SB ,","place":["UK"]},{"name":"Institute for Neuroscience and Cardiovascular Research, University of Edinburgh , Edinburgh, EH16 4TJ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isaac","family":"Chau","sequence":"additional","affiliation":[{"name":"Anne Rowling Regenerative Neurology Clinic, University of Edinburgh , Edinburgh, EH16 4SB ,","place":["UK"]},{"name":"Euan MacDonald Centre for Motor Neuron Disease Research, University of Edinburgh , Edinburgh, EH16 4SB ,","place":["UK"]},{"name":"Institute for Neuroscience and Cardiovascular Research, University of Edinburgh , Edinburgh, EH16 4TJ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chloe","family":"Parker","sequence":"additional","affiliation":[{"name":"Anne Rowling Regenerative Neurology Clinic, University of Edinburgh , Edinburgh, EH16 4SB ,","place":["UK"]},{"name":"Euan MacDonald Centre for Motor Neuron Disease Research, University of Edinburgh , Edinburgh, EH16 4SB ,","place":["UK"]},{"name":"Institute for Neuroscience and Cardiovascular Research, University of Edinburgh , Edinburgh, EH16 4TJ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hatice","family":"Kurucu King","sequence":"additional","affiliation":[{"name":"Anne Rowling Regenerative Neurology Clinic, University of Edinburgh , Edinburgh, EH16 4SB ,","place":["UK"]},{"name":"Euan MacDonald Centre for Motor Neuron Disease Research, University of Edinburgh , Edinburgh, EH16 4SB ,","place":["UK"]},{"name":"Institute for Neuroscience and Cardiovascular Research, University of Edinburgh , Edinburgh, EH16 4TJ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johnny","family":"Tam","sequence":"additional","affiliation":[{"name":"Anne Rowling Regenerative Neurology Clinic, University of Edinburgh , Edinburgh, EH16 4SB ,","place":["UK"]},{"name":"Euan MacDonald Centre for Motor Neuron Disease Research, University of Edinburgh , Edinburgh, EH16 4SB ,","place":["UK"]},{"name":"Institute for Neuroscience and Cardiovascular Research, University of Edinburgh , Edinburgh, EH16 4TJ ,","place":["UK"]},{"name":"UK Dementia Research Institute, University of Edinburgh , Edinburgh, EH16 4SB 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Neuron Disease Research, University of Edinburgh , Edinburgh, EH16 4SB ,","place":["UK"]},{"name":"Institute for Neuroscience and Cardiovascular Research, University of Edinburgh , Edinburgh, EH16 4TJ ,","place":["UK"]},{"name":"UK Dementia Research Institute, University of Edinburgh , Edinburgh, EH16 4SB ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Baxter","sequence":"additional","affiliation":[{"name":"Anne Rowling Regenerative Neurology Clinic, University of Edinburgh , Edinburgh, EH16 4SB ,","place":["UK"]},{"name":"Euan MacDonald Centre for Motor Neuron Disease Research, University of Edinburgh , Edinburgh, EH16 4SB ,","place":["UK"]},{"name":"Institute for Neuroscience and Cardiovascular Research, University of Edinburgh , Edinburgh, EH16 4TJ ,","place":["UK"]},{"name":"UK Dementia Research Institute, University of Edinburgh , Edinburgh, EH16 4SB 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Gothenburg , M\u00f6lndal, SE-413 45 ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David P J","family":"Hunt","sequence":"additional","affiliation":[{"name":"Anne Rowling Regenerative Neurology Clinic, University of Edinburgh , Edinburgh, EH16 4SB ,","place":["UK"]},{"name":"Euan MacDonald Centre for Motor Neuron Disease Research, University of Edinburgh , Edinburgh, EH16 4SB ,","place":["UK"]},{"name":"Institute for Neuroscience and Cardiovascular Research, University of Edinburgh , Edinburgh, EH16 4TJ ,","place":["UK"]},{"name":"UK Dementia Research Institute, University of Edinburgh , Edinburgh, EH16 4SB ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhuvaneish","family":"Thangaraj Selvaraj","sequence":"additional","affiliation":[{"name":"Anne Rowling Regenerative Neurology Clinic, University of Edinburgh , Edinburgh, EH16 4SB ,","place":["UK"]},{"name":"Euan MacDonald Centre for Motor Neuron Disease 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