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Plasma and CSF neurofilament light chain distinguish neurodegenerative from primary psychiatric conditions in a clinical setting

Eratne D 1 , Kang MJY 1 , Lewis C 1 , Dang C 2 , Malpas CB 3 , Keem M 4 Show all authors , Grewal J 5 , Marinov V 1 , Coe A 6 , Kaylor-Hughes C 6 , Borchard T 7 , Keng-Hong C 1 , Waxmann A 1 , Saglam B 1 , Kalincik T 8 , Kanaan R 9 , Kelso W 1 , Evans A 1 , Farrand S 1 , Loi S 1 , Walterfang M 1 , Stehmann C 10 , Li QX 10 , Collins S 10 , Masters CL 10 , Santillo AF 11 , Zetterberg H 12 , Blennow K 13 , Berkovic SF 14 , Velakoulis D 1 , MiND Study Group

Affiliations 

  • 1 Neuropsychiatry Centre, The Royal Melbourne Hospital, Melbourne, Victoria, Australia
  • 2 National Ageing Research Institute, Melbourne, Victoria, Australia
  • 3 Department of Medicine (Royal Melbourne Hospital), University of Melbourne, Melbourne, Victoria, Australia
  • 4 School of Rural Health, Monash University, Melbourne, Victoria, Australia
  • 5 Alfred Mental and Addiction Health, Alfred Health, Melbourne, Victoria, Australia
  • 6 Department of General Practice, The University of Melbourne, Melbourne, Victoria, Australia
  • 7 Ramsay Clinic Northside, Frederick St, Sydney, Australia
  • 8 Neuroimmunology Centre, Department of Neurology, Royal Melbourne Hospital, Melbourne, Victoria, Australia
  • 9 Department of Psychiatry, The University of Melbourne, Austin Hospital, Melbourne, Victoria, Australia
  • 10 The Florey, Melbourne, Victoria, Australia
  • 11 Department of Clinical Sciences, Clinical Memory Research Unit, Faculty of Medicine, Lund University, Malmö, Sweden
  • 12 Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden
  • 13 Institute of Neuroscience and Physiology, University of Gothenburg, Mölndal, Sweden
  • 14 Epilepsy Research Centre, Department of Medicine, Austin Health, The University of Melbourne, Melbourne, Victoria, Australia
Alzheimers Dement, 2024 Nov;20(11):7989-8001.
PMID: 39369278 DOI: 10.1002/alz.14278

Abstract

INTRODUCTION: People with neurodegenerative disorders (ND) frequently face diagnostic delay and misdiagnosis. We investigated blood and cerebrospinal fluid (CSF) neurofilament light chain (NfL) to distinguish ND from primary psychiatric disorders (PPD), a common challenge in clinical settings.

METHODS: Plasma and CSF NfL levels were measured and compared between groups, adjusting for age, sex, and weight.

RESULTS: A total of 337 participants were included: 136 ND, 77 PPD, and 124 Controls. Plasma NfL was 2.5-fold elevated in ND compared to PPD and had strong diagnostic performance (area under the curve, [AUC]: 0.86, 81%/85% specificity/sensitivity) that was comparable to CSF NfL (2-fold elevated, AUC: 0.89, 95%/71% specificity/sensitivity). Diagnostic performance was especially strong in younger people (40- 

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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