路易氏体型失智症
生物标志物
蛋白质组
痴呆
医学
阿尔茨海默病
疾病
脑脊液
病理
失智症
多路复用
生物信息学
肿瘤科
内科学
生物
遗传学
作者
Marta del Campo,Lisa Vermunt,Carel F.W. Peeters,Anne Sieben,Yanaika S. Hok‐A‐Hin,Alberto Lleó,Daniel Alcolea,Mirrelijn M. van Nee,Sebastiaan Engelborghs,Juliette L. van Alphen,Sanaz Arezoumandan,Alice Chen‐Plotkin,David J. Irwin,Wiesje M. van der Flier,Afina W. Lemstra,Charlotte E. Teunissen
标识
DOI:10.1038/s41467-023-41122-y
摘要
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.
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