CSF proteome profiling reveals biomarkers to discriminate dementia with Lewy bodies from Alzheimer´s disease

Marta Campo (), Lisa Vermunt, Carel F. W. Peeters, Anne Sieben, Yanaika S. Hok-A-Hin, Alberto Lleó, Daniel Alcolea, Mirrelijn Nee, Sebastiaan Engelborghs, Juliette L. Alphen, Sanaz Arezoumandan, Alice Chen-Plotkin, David J. Irwin, Wiesje M. Flier, Afina W. Lemstra and Charlotte E. Teunissen
Additional contact information
Marta Campo: Amsterdam University Medical Centers, Location VUmc
Lisa Vermunt: Amsterdam University Medical Centers, Location VUmc
Carel F. W. Peeters: Wageningen University & Research
Anne Sieben: Antwerp University
Yanaika S. Hok-A-Hin: Amsterdam University Medical Centers, Location VUmc
Alberto Lleó: Institut d’Investigacions Biomèdiques Sant Pau (IIB SANT PAU) - Hospital de Sant Pau, Universitat Autònoma de Barcelona, Hospital de la Santa Creu i Sant Pau
Daniel Alcolea: Institut d’Investigacions Biomèdiques Sant Pau (IIB SANT PAU) - Hospital de Sant Pau, Universitat Autònoma de Barcelona, Hospital de la Santa Creu i Sant Pau
Mirrelijn Nee: Amsterdam University Medical Centers, Location VUmc
Sebastiaan Engelborghs: University of Antwerp
Juliette L. Alphen: Amsterdam University Medical Centers, Location VUmc
Sanaz Arezoumandan: University of Pennsylvania
Alice Chen-Plotkin: University of Pennsylvania
David J. Irwin: University of Pennsylvania
Wiesje M. Flier: Amsterdam University Medical Centers, Location VUmc
Afina W. Lemstra: Amsterdam University Medical Centers, Location VUmc
Charlotte E. Teunissen: Amsterdam University Medical Centers, Location VUmc

Nature Communications, 2023, vol. 14, issue 1, 1-14

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-41122-y

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