CSF proteome profiling reveals biomarkers to discriminate dementia with Lewy bodies from Alzheimer's disease
Campo Milán, Marta del (Universidad CEU San Pablo)
Vermunt, Lisa (Amsterdam University Medical Center (UMC))
Peeters, Carel F.W. (Wageningen University & Research)
Sieben, Anne (Antwerp University)
Hok-A-Hin, Yanaika S. (Amsterdam University Medical Center (UMC))
Lleó, Alberto (Institut d'Investigació Biomèdica Sant Pau)
Alcolea, Daniel (Institut d'Investigació Biomèdica Sant Pau)
van Nee, Mirrelijn (Amsterdam University Medical Center (UMC))
Engelborghs, Sebastiaan (Universitair Ziekenhuis Brussel)
van Alphen, Juliette L. (Amsterdam University Medical Center (UMC))
Arezoumandan, Sanaz (University of Pennsylvania)
Chen-Plotkin, Alice (University of Pennsylvania)
Irwin, David J. (University of Pennsylvania)
van der Flier, Wiesje M. (Amsterdam University Medical Center (UMC))
Lemstra, Afina W. (Amsterdam University Medical Center (UMC))
Teunissen, Charlotte E. (Amsterdam University Medical Center (UMC))
Universitat Autònoma de Barcelona

Date:	2023
Abstract:	Diagnosis of dementia with Lewy bodies (DLB) is challenging and specific biofluid biomarkers are highly needed. We employed proximity extension-based assays to measure 665 proteins in the cerebrospinal fluid (CSF) from patients with DLB (n = 109), Alzheimer's disease (AD, n = 235) and cognitively unimpaired controls (n = 190). We identified over 50 CSF proteins dysregulated in DLB, enriched in myelination processes among others. The dopamine biosynthesis enzyme DDC was the strongest dysregulated protein, and could efficiently discriminate DLB from controls and AD (AUC:0. 91 and 0. 81 respectively). Classification modeling unveiled a 7-CSF biomarker panel that better discriminate DLB from AD (AUC:0. 93). A custom multiplex panel for six of these markers (DDC, CRH, MMP-3, ABL1, MMP-10, THOP1) was developed and validated in independent cohorts, including an AD and DLB autopsy cohort. This DLB CSF proteome study identifies DLB-specific protein changes and translates these findings to a practicable biomarker panel that accurately identifies DLB patients, providing promising diagnostic and clinical trial testing opportunities.
Grants:	Instituto de Salud Carlos III PI18/00435 Instituto de Salud Carlos III PI20/01330 Agencia Estatal de Investigación PID2020-115613RA-I00
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Alzheimer Disease ; Autopsy ; Biomarkers ; Humans ; Lewy Body Disease ; Proteome
Published in:	Nature communications, Vol. 14 Núm. 1 (december 2023) , p. 5635, ISSN 2041-1723

DOI: 10.1038/s41467-023-41122-y
PMID: 37704597

14 p, 13.9 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
Articles > Published articles