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Journal Article Ppublish 1 citation

PubMed: 40145305 DOI: 10.1002/alz.70116

Novel blood-based proteomic signatures across multiple neurodegenerative diseases.

Alzheimers Dement 21(3):e70116

Authors: Robert Durcan, Amanda Heslegrave, Peter Swann, Julia Goddard, Leonidas Chouliaras, Alexander G Murley, George Savulich, W Richard Bevan-Jones, Owen Swann, Nicholas J Ashton, Kaj Blennow, William McEwan, Henrik Zetterberg, James B Rowe, John T O'Brien, Maura Malpetti

Affiliations

  • Department of Clinical Neurosciences, University of Cambridge and Cambridge University Hospitals NHS Trust, Cambridge, UK.
  • UK Dementia Research Institute, University College London, London, UK.
  • Department of Psychiatry, University of Cambridge, Cambridge, UK.
  • Department of Clinical Neurosciences, University of Cambridge and Cambridge University Hospitals NHS Trust, Cambridge, UK. UK Dementia Research Institute, University of Cambridge, Cambridge, UK.
  • Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden. Banner Alzheimer's Institute, University of Arizona, Phoenix, Arizona, USA. Banner Sun Health Research Institute, Sun City, Arizona, USA.
  • Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden.
  • Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
  • UK Dementia Research Institute, University of Cambridge, Cambridge, UK.
  • UK Dementia Research Institute, University College London, London, UK. Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden. Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden. Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK. Hong Kong Center for Neurodegenerative Diseases, Hong Kong, China. Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.
  • Medical Research Council Cognition and Brain Sciences Unit, University of Cambridge, Cambridge, UK.

Abstract

INTRODUCTION

Blood-based biomarkers have the potential to support early and accurate diagnoses of neurodegenerative diseases, which are sensitive to molecular pathology and are predictive of outcome. We evaluated a novel multiplex proteomic method in people with diverse neurodegenerative diseases.

METHODS

Serum from people with Alzheimer's disease (N = 36), Lewy body dementia (N = 34), frontotemporal dementia (N = 36), and progressive supranuclear palsy (N = 36) and age-matched controls (N = 30) was analyzed with the nucleic acid linked immuno-sandwich assay (NULISA) central nervous system panel (≈ 120 analytes) and inflammation panel (250 analytes). Biomarkers were compared across groups and included as predictors of survival.

RESULTS

The NULISA panels demonstrated high sensitivity and reliability for detecting multiple biomarkers across neurodegenerative disorders. There were condition-specific proteomic biomarkers, while neurofilament light chain, corticotropin-releasing hormone, CD276, and a data-driven inflammation pattern were significant transdiagnostic outcome predictors.

DISCUSSION

The sensitive NULISA multiplex approach supports differential diagnosis and target identification, with prognostically informative dementia-related biomarkers.

HIGHLIGHTS

We tested the novel technology nucleic acid linked immuno-sandwich assay (NULISA) in people with diverse neurodegenerative diseases, which demonstrated high sensitivity and reliability for detecting multiple biomarkers in serum samples. We compared the NULISA central nervous system serum results to single molecule array (Simoa) plasma assays for phosphorylated tau (p-tau)217, p-tau231, neurofilament light chain (NfL), and glial fibrillary acidic protein, finding strong correlations. Increased levels of serum NfL were identified across all patient groups and most elevated in the frontotemporal dementia (FTD) and progressive supranuclear palsy (PSP) cohorts, while p-tau epitopes were the most significant markers in patients with Alzheimer's disease (AD) and Lewy body dementia. Patients with FTD and PSP showed upregulation of many inflammation markers, compared to controls and patients with AD. We found condition-specific proteomic biomarkers, while NfL, corticotropin-releasing hormone, CD276, and data-driven immune signatures were significant transdiagnostic predictors of clinical outcomes (survival rates).

MeSH

Dementia, Supranuclear Palsy, Progressive, Corticotropin-Releasing Hormone, Blood, Serum, Frontotemporal Dementia, Alzheimer Disease, Biomarkers, Central Nervous System, Hormones, Nucleic Acids, Diagnosis, Nervous System, Paralysis, Adrenocorticotropic Hormone, Neurodegenerative Diseases

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