TY - JOUR
T1 - CSF proteome profiling reveals biomarkers to discriminate dementia with Lewy bodies from Alzheimer´s disease
AU - del Campo, Marta
AU - Vermunt, Lisa
AU - Peeters, Carel F. W.
AU - Sieben, Anne
AU - Hok-A-Hin, Yanaika S.
AU - Lleó, Alberto
AU - Alcolea, Daniel
AU - van Nee, Mirrelijn
AU - Engelborghs, Sebastiaan
AU - van Alphen, Juliette L.
AU - Arezoumandan, Sanaz
AU - Chen-Plotkin, Alice
AU - Irwin, David J.
AU - van der Flier, Wiesje M.
AU - Lemstra, Afina W.
AU - Teunissen, Charlotte E.
N1 - Funding Information: M.C. has been an invited speaker at Eisai, is an associate editor at Alzheimer´s Research & Therapy and has been an invited writer for Springer Healthcare. L.V. received a grant for CORAL consortium by Olink. D.I. is a Scientific Advisory Board Member for Denali Therapeutics. D.A. participated in advisory boards from Fujirebio-Europe and Roche Diagnostics and received speaker honoraria from Fujirebio-Europe, Roche Diagnostics, Nutricia, Krka Farmacéutica S.L., Zambon S.A.U. and Esteve Pharmaceuticals S.A. D.A., and A.L. declare a filed patent application (Title: Markers of synaptopathy in neurodegenerative disease; Applicant: Fundació Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau, Inventors: Olivia BELBIN; Alberto LLEÓ; Alejandro BAYÉS; Juan FORTEA; Daniel ALCOLEA; Application number: PCT/EP2019/056535; International Publication Number: WO 2019/175379 A1; Current status: Active. Licensed to ADx Neurociences NV (Ghent, Belgium); This patent is not related to any specific aspect of the current manuscript). W.F. has performed contract research for Biogen MA Inc, and Boehringer Ingelheim. W.F. has been an invited speaker at Boehringer Ingelheim, Biogen MA Inc, Danone, Eisai, WebMD Neurology (Medscape), Springer Healthcare. W.F. is consultant to Oxford Health Policy Forum CIC, Roche, and Biogen MA Inc. WF participated in advisory boards of Biogen MA Inc and Roche. All funding is paid to her institution. W.F. is a member of the steering committee of PAVE, and Think Brain Health. WF was associate editor of Alzheimer, Research & Therapy in 2020/2021. W.F. is an associate editor at Brain. C.E.T. has a collaboration contract with ADx Neurosciences, Quanterix and Eli Lilly, performed contract research or received grants from AC-Immune, Axon Neurosciences, Bioconnect, Bioorchestra, Brainstorm Therapeutics, Celgene, EIP Pharma, Eisai, Grifols, Novo Nordisk, PeopleBio, Roche, Toyama, Vivoryon. She serves on editorial boards of Medidact Neurologie/Springer, Alzheimer Research and Therapy, Neurology: Neuroimmunology & Neuroinflammation, and is editor of a Neuromethods book Springer. She had speaker contracts for Roche, Grifols, Novo Nordisk. The rest of the authors declare no competing interest. Publisher Copyright: © 2023, Springer Nature Limited.
PY - 2023/12/1
Y1 - 2023/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85171152545&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/s41467-023-41122-y
DO - https://doi.org/10.1038/s41467-023-41122-y
M3 - Article
C2 - 37704597
SN - 2041-1723
VL - 14
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 5635
ER -