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.
PY - 2023/12
Y1 - 2023/12
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.
U2 - 10.1038/s41467-023-41122-y
DO - 10.1038/s41467-023-41122-y
M3 - Article
C2 - 37704597
AN - SCOPUS:85171152545
SN - 2041-1723
VL - 14
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 5635
ER -