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

biomarkers dementia diagnosis neurofilament light chain protein psychiatric disorders

Journal

Alzheimer's & dementia : the journal of the Alzheimer's Association
ISSN: 1552-5279
Titre abrégé: Alzheimers Dement
Pays: United States
ID NLM: 101231978

Informations de publication

Date de publication:
06 Oct 2024
Historique:
revised: 29 08 2024
received: 12 08 2024
accepted: 31 08 2024
medline: 6 10 2024
pubmed: 6 10 2024
entrez: 6 10 2024
Statut: aheadofprint

Résumé

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. Plasma and CSF NfL levels were measured and compared between groups, adjusting for age, sex, and weight. 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- < 60 years). Additional findings were cutoffs optimized for sensitivity and specificity, and issues important for future clinical translation. This study adds important evidence for a simple blood-based biomarker to assist as a screening test for neurodegeneration and distinction from PPD, in clinical settings. NfL levels were significantly higher in ND versus PPD. Plasma NfL showed strong diagnostic performance, comparable to CSF NfL, to distinguish ND from PPD. Diagnostic performance was higher in younger people, where diagnostic challenges are greater. Further research is needed on analytical and reference range factors, for clinical translation. These findings support a simple screening blood test for neurodegeneration.

Identifiants

DOI: 10.1002/alz.14278 PMID: 39369278
pubmed: 39369278
doi: 10.1002/alz.14278
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Swedish Research Council
ID : #2023-00356
Organisme : Swedish Research Council
ID : #2022-01018
Organisme : Swedish Research Council
ID : #2019-02397
Organisme : European Union's Horizon Europe research and innovation programme
ID : 101053962
Organisme : Swedish State Support for Clinical Research
ID : #ALFGBG-71320
Organisme : Department of Psychiatry
Organisme : University of Melbourne
Organisme : Ramsay Hospital Research Foundation
Organisme : Australian Commonwealth Government
Organisme : NHMRC
ID : 1185180

Informations de copyright

© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.

Références

Loi SM, Goh AMY, Mocellin R, et al. Time to diagnosis in younger‐onset dementia and the impact of a specialist diagnostic service. Int Psychogeriatr. 2022;34:367‐375. doi:10.1017/S1041610220001489
Tsoukra P, Velakoulis D, Wibawa P, et al. The diagnostic challenge of young‐onset dementia syndromes and primary psychiatric diseases: results from a retrospective 20‐year cross‐sectional study. J Neuropsychiatry Clin Neurosci. 2022;34:44‐52. doi:10.1176/appi.neuropsych.20100266
Kang MJY, Eratne D, Dobson H, et al. Cerebrospinal fluid neurofilament light predicts longitudinal diagnostic change in patients with psychiatric and neurodegenerative disorders. Acta Neuropsychiatr. 2024;36(1):17‐28. doi:10.1017/neu.2023.25
Eratne D, Loi SM, Walia N, et al. A pilot study of the utility of cerebrospinal fluid neurofilament light chain in differentiating neurodegenerative from psychiatric disorders: a “C‐reactive protein” for psychiatrists and neurologists?. Aust N Z J Psychiatry. 2020;54:57‐67. doi:10.1177/0004867419857811
Eratne D, Loi SM, Li Q‐X, et al. Cerebrospinal fluid neurofilament light chain differentiates primary psychiatric disorders from rapidly progressive, Alzheimer's disease and frontotemporal disorders in clinical settings. Alzheimers Dement. 2022;18:2218‐2233. doi:10.1002/alz.12549
Eratne D, Loi SM, Li QX, et al. Cerebrospinal fluid neurofilament light chain is elevated in Niemann–Pick type C compared to psychiatric disorders and healthy controls and may be a marker of treatment response. Aust N Z J Psychiatry. 2020;54:648‐649. doi:10.1177/0004867419893431
Eratne D, Keem M, Lewis C, et al. Cerebrospinal fluid neurofilament light chain differentiates behavioural variant frontotemporal dementia progressors from non‐progressors. J Neurol Sci. 2022;442:120439. doi:10.1016/j.jns.2022.120439
Karantali E, Kazis D, Chatzikonstantinou S, Petridis F, Mavroudis I. The role of neurofilament light chain in frontotemporal dementia: a meta‐analysis. Aging Clin Exp Res. 2021;33(4):869‐881. doi:10.1007/s40520‐020‐01554‐8
Davy V, Dumurgier J, Fayosse A, Paquet C, Cognat E. Neurofilaments as emerging biomarkers of neuroaxonal damage to differentiate behavioral frontotemporal dementia from primary psychiatric disorders: a systematic review. Diagnostics. 2021;11:754. doi:10.3390/diagnostics11050754
Forgrave LM, Ma M, Best JR, DeMarco ML. The diagnostic performance of neurofilament light chain in CSF and blood for Alzheimer's disease, frontotemporal dementia, and amyotrophic lateral sclerosis: a systematic review and meta‐analysis. Alzheimers Dement. 2019;11:730‐743. doi:10.1016/j.dadm.2019.08.009
Santos F, Cabreira V, Rocha S, Massano J. Blood biomarkers for the diagnosis of neurodegenerative dementia: a systematic review. J Geriatr Psychiatry Neurol. 2023;36:267‐281. doi:10.1177/08919887221141651
Wang S‐Y, Chen W, Xu W, et al. Neurofilament light chain in cerebrospinal fluid and blood as a biomarker for neurodegenerative diseases: a systematic review and meta‐analysis. J Alzheimers Dis. 2019;72:1353‐1361. doi:10.3233/JAD‐190615
Ashton NJ, Janelidze S, Al Khleifat A, et al. A multicentre validation study of the diagnostic value of plasma neurofilament light. Nat Commun. 2021;12:3400. doi:10.1038/s41467‐021‐23620‐z
Götze K, Vrillon A, Bouaziz‐Amar E, et al. Plasma neurofilament light chain in memory clinic practice: evidence from a real‐life study. Neurobiol Dis. 2023;176:105937. doi:10.1016/j.nbd.2022.105937
Niikado M, Chrem‐Méndez P, Itzcovich T, et al. Evaluation of cerebrospinal fluid neurofilament light chain as a routine biomarker in a memory clinic. J Gerontol A Biol Sci Med Sci. 2019;74:442‐445. doi:10.1093/gerona/gly179
Sarto J, Ruiz‐García R, Guillén N, et al. Diagnostic performance and clinical applicability of blood‐based biomarkers in a prospective memory clinic cohort. Neurology. 2023;100:e860‐873. doi:10.1212/WNL.0000000000201597
Verberk IMW, Laarhuis MB, van den Bosch KA, et al. Serum markers glial fibrillary acidic protein and neurofilament light for prognosis and monitoring in cognitively normal older people: a prospective memory clinic‐based cohort study. Lancet Healthy Longev 2021;2:e87‐95. doi:10.1016/S2666‐7568(20)30061‐1
Vrillon A, Ashton NJ, Karikari TK, et al. Comparison of CSF and plasma NfL and pNfH for Alzheimer's disease diagnosis: a memory clinic study. J Neurol. 2024;271:1297‐1310. doi:10.1007/s00415‐023‐12066‐6
Gleerup HS, Simonsen AH, Høgh P. The added value of cerebrospinal fluid neurofilament light chain to existing diagnostic methods and biomarkers in a mixed memory clinic cohort of consecutive patients. J Alzheimers Dis Rep. 2022;6:121‐127. doi:10.3233/ADR‐210047
Willemse EAJ, Scheltens P, Teunissen CE, Vijverberg EGB. A neurologist's perspective on serum neurofilament light in the memory clinic: a prospective implementation study. Alzheimers Res Therapy. 2021;13:101. doi:10.1186/s13195‐021‐00841‐4
Light V, Jones SL, Rahme E, et al. Clinical accuracy of serum neurofilament light to differentiate frontotemporal dementia from primary psychiatric disorders is age‐dependent. Am J Geriatr Psychiatry. 2024;32:988‐1001. doi:10.1016/j.jagp.2024.03.008
Eratne D, Kang M, Malpas C, et al. Plasma neurofilament light in behavioural variant frontotemporal dementia compared to mood and psychotic disorders. Aust N Z J Psychiatry. 2024;58:70‐81. doi:10.1177/00048674231187312
Katisko K, Cajanus A, Jääskeläinen O, et al. Serum neurofilament light chain is a discriminative biomarker between frontotemporal lobar degeneration and primary psychiatric disorders. J Neurol. 2020;267:162‐167. doi:10.1007/s00415‐019‐09567‐8
Al Shweiki MR, Steinacker P, Oeckl P, et al. Neurofilament light chain as a blood biomarker to differentiate psychiatric disorders from behavioural variant frontotemporal dementia. J Psychiatr Res. 2019;113:137‐140. doi:10.1016/j.jpsychires.2019.03.019
Arslan B, Zetterberg H. Neurofilament light chain as neuronal injury marker – what is needed to facilitate implementation in clinical laboratory practice?. Clin Chem Lab Med. 2023;61:1140‐1149. doi:10.1515/cclm‐2023‐0036
Coppens S, Lehmann S, Hopley C, Hirtz C. Neurofilament‐light, a promising biomarker: analytical, metrological and clinical challenges. Int J Mol Sci. 2023;24:11624. doi:10.3390/ijms241411624
Bavato F, Barro C, Schnider LK, et al. Introducing neurofilament light chain measure in psychiatry: current evidence, opportunities, and pitfalls. Mol Psychiatry. 2024;29:2543‐2559. doi:10.1038/s41380‐024‐02524‐6
Sotirchos ES, Hu C, Smith MD, et al. Agreement between published reference resources for neurofilament light chain levels in people with multiple sclerosis. Neurology. 2023;101(23):e2448‐e2453. doi:10.1212/WNL.0000000000207957
Benkert P, Meier S, Schaedelin S, et al. Serum neurofilament light chain for individual prognostication of disease activity in people with multiple sclerosis: a retrospective modelling and validation study. Lancet Neurol. 2022;21:246‐257. doi:10.1016/S1474‐4422(22)00009‐6
Brum WS, Cullen NC, Janelidze S, et al. A two‐step workflow based on plasma p‐tau217 to screen for amyloid β positivity with further confirmatory testing only in uncertain cases. Nat Aging. 2023;3:1079‐1090. doi:10.1038/s43587‐023‐00471‐5
Simrén J, Andreasson U, Gobom J, et al. Establishment of reference values for plasma neurofilament light based on healthy individuals aged 5‐90 years. Brain Commun. 2022;4:fcac174. doi:10.1093/braincomms/fcac174
Draper B, Cations M, White F, et al. Time to diagnosis in young‐onset dementia and its determinants: the INSPIRED study. Int J Geriatr Psychiatry. 2016;31:1217‐1224. doi:10.1002/gps.4430
Rossor MN, Fox NC, Mummery CJ, Schott JM, Warren JD. The diagnosis of young‐onset dementia. Lancet Neurol. 2010;9:793‐806. doi:10.1016/S1474‐4422(10)70159‐9
Eratne D, Li Q‐X, Lewis C, et al. Diagnostic utility of plasma ptau217, ptau181, GFAP for Alzheimer disease in a heterogeneous younger onset dementia clinical cohort 2024:2024.04.29.24306586. medRxiv. 2024. doi:10.1101/2024.04.29.24306586
Ashton NJ, Brum WS, Di Molfetta G, et al. Diagnostic accuracy of a plasma phosphorylated tau 217 immunoassay for Alzheimer disease pathology. JAMA Neurol. 2024;81(3):255‐263. doi:10.1001/jamaneurol.2023.5319
Khalil M, Teunissen CE, Lehmann S, et al. Neurofilaments as biomarkers in neurological disorders—towards clinical application. Nat Rev Neurol. 2024:20;1‐19. doi:10.1038/s41582‐024‐00955‐x
Khalil M, Teunissen CE, Otto M, et al. Neurofilaments as biomarkers in neurological disorders. Nat Rev Neurol. 2018;14:577‐589. doi:10.1038/s41582‐018‐0058‐z
Gaetani L, Blennow K, Calabresi P, Di Filippo M, Parnetti L, Zetterberg H. Neurofilament light chain as a biomarker in neurological disorders. J Neurol Neurosurg Psychiatry. 2019;90:870‐881. doi:10.1136/jnnp‐2018‐320106
Gao W, Zhang Z, Lv X, et al. Neurofilament light chain level in traumatic brain injury: a system review and meta‐analysis. Medicine. 2020;99:e22363. doi:10.1097/MD.0000000000022363
Krogseth M, Davis D, Jackson TA, et al. Delirium, neurofilament light chain, and progressive cognitive impairment: analysis of a prospective Norwegian population‐based cohort. Lancet Healthy Longev. 2023;4:e399‐408. doi:10.1016/S2666‐7568(23)00098‐3
Abu‐Rumeileh S, Abdelhak A, Foschi M, et al. The multifaceted role of neurofilament light chain protein in non‐primary neurological diseases. Brain. 2022;146:421‐437. doi:10.1093/brain/awac328
Loi SM, Eratne D, Goh AMY, et al. A 10 year retrospective cohort study of inpatients with younger‐onset dementia. Int J Geriatr Psychiatry. 2021;36:294‐301. doi:10.1002/gps.5424

Auteurs

Dhamidhu Eratne (D)

Neuropsychiatry Centre, The Royal Melbourne Hospital, Melbourne, Victoria, Australia.
Department of Psychiatry, The University of Melbourne, Melbourne, Victoria, Australia.
The Florey, Melbourne, Victoria, Australia.
ORCID: 0000-0002-3226-7645

Matthew J Y Kang (MJY)

Neuropsychiatry Centre, The Royal Melbourne Hospital, Melbourne, Victoria, Australia.
Department of Psychiatry, The University of Melbourne, Melbourne, Victoria, Australia.

Courtney Lewis (C)

Neuropsychiatry Centre, The Royal Melbourne Hospital, Melbourne, Victoria, Australia.
Department of Psychiatry, The University of Melbourne, Melbourne, Victoria, Australia.
Institute of Health and Wellbeing, Federation University, Melbourne, Victoria, Australia.

Christa Dang (C)

National Ageing Research Institute, Melbourne, Victoria, Australia.
Department of General Practice, The University of Melbourne, Melbourne, Victoria, Australia.

Charles B Malpas (CB)

Department of Medicine (Royal Melbourne Hospital), University of Melbourne, Melbourne, Victoria, Australia.
Melbourne School of Psychological Sciences, University of Melbourne, Melbourne, Victoria, Australia.

Michael Keem (M)

School of Rural Health, Monash University, Melbourne, Victoria, Australia.
Melbourne School of Population & Global Health and Department of Medical Education, University of Melbourne, Melbourne, Victoria, Australia.
Western Health, St. Albans, Victoria, Australia.
Mildura Base Public Hospital, Melbourne, Victoria, Australia.

Jasleen Grewal (J)

Alfred Mental and Addiction Health, Alfred Health, Melbourne, Victoria, Australia.

Vladimir Marinov (V)

Neuropsychiatry Centre, The Royal Melbourne Hospital, Melbourne, Victoria, Australia.

Amy Coe (A)

Department of General Practice, The University of Melbourne, Melbourne, Victoria, Australia.

Cath Kaylor-Hughes (C)

Department of General Practice, The University of Melbourne, Melbourne, Victoria, Australia.

Thomas Borchard (T)

Ramsay Clinic Northside, Frederick St, Sydney, Australia.

Chhoa Keng-Hong (C)

Neuropsychiatry Centre, The Royal Melbourne Hospital, Melbourne, Victoria, Australia.
Department of Psychiatry & Mental Health, Sarawak General Hospital, Kuching, Sarawak, Malaysia.

Alexandra Waxmann (A)

Neuropsychiatry Centre, The Royal Melbourne Hospital, Melbourne, Victoria, Australia.

Burcu Saglam (B)

Neuropsychiatry Centre, The Royal Melbourne Hospital, Melbourne, Victoria, Australia.

Tomas Kalincik (T)

Neuroimmunology Centre, Department of Neurology, Royal Melbourne Hospital, Melbourne, Victoria, Australia.
CORe, Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia.

Richard Kanaan (R)

Department of Psychiatry, The University of Melbourne, Austin Hospital, Melbourne, Victoria, Australia.

Wendy Kelso (W)

Neuropsychiatry Centre, The Royal Melbourne Hospital, Melbourne, Victoria, Australia.

Andrew Evans (A)

Neuropsychiatry Centre, The Royal Melbourne Hospital, Melbourne, Victoria, Australia.

Sarah Farrand (S)

Neuropsychiatry Centre, The Royal Melbourne Hospital, Melbourne, Victoria, Australia.

Samantha Loi (S)

Neuropsychiatry Centre, The Royal Melbourne Hospital, Melbourne, Victoria, Australia.
Department of Psychiatry, The University of Melbourne, Melbourne, Victoria, Australia.

Mark Walterfang (M)

Neuropsychiatry Centre, The Royal Melbourne Hospital, Melbourne, Victoria, Australia.
Department of Psychiatry, The University of Melbourne, Melbourne, Victoria, Australia.

Christiane Stehmann (C)

The Florey, Melbourne, Victoria, Australia.

Qiao-Xin Li (QX)

The Florey, Melbourne, Victoria, Australia.

Steven Collins (S)

The Florey, Melbourne, Victoria, Australia.

Colin L Masters (CL)

The Florey, Melbourne, Victoria, Australia.

Alexander F Santillo (AF)

Department of Clinical Sciences, Clinical Memory Research Unit, Faculty of Medicine, Lund University, Malmö, Sweden.

Henrik Zetterberg (H)

Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK.
UK Dementia Research Institute at UCL, 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.

Kaj Blennow (K)

Institute of Neuroscience and Physiology, University of Gothenburg, Mölndal, Sweden.
Clinical Neurochemistry Lab, Sahlgrenska University Hospital, Mölndal, Sweden.
Paris Brain Institute, ICM, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France.
Neurodegenerative Disorder Research Center, Division of Life Sciences and Medicine, and Department of Neurology, Institute on Aging and Brain Disorders, University of Science and Technology of China and First Affiliated Hospital of USTC, Hefei, Anhui, P.R. China.

Samuel F Berkovic (SF)

Epilepsy Research Centre, Department of Medicine, Austin Health, The University of Melbourne, Melbourne, Victoria, Australia.

Dennis Velakoulis (D)

Neuropsychiatry Centre, The Royal Melbourne Hospital, Melbourne, Victoria, Australia.
Department of Psychiatry, The University of Melbourne, Melbourne, Victoria, Australia.

Classifications MeSH