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

被引:25
作者
del Campo, Marta [1 ,2 ,3 ,4 ]
Vermunt, Lisa [1 ,2 ,5 ]
Peeters, Carel F. W. [6 ]
Sieben, Anne [7 ]
Hok-A-Hin, Yanaika S. [1 ,2 ]
Lleo, Alberto [8 ,9 ]
Alcolea, Daniel [8 ,9 ]
van Nee, Mirrelijn [10 ]
Engelborghs, Sebastiaan [11 ,12 ,13 ]
van Alphen, Juliette L. [5 ]
Arezoumandan, Sanaz [14 ]
Chen-Plotkin, Alice [14 ]
Irwin, David J. [14 ]
van der Flier, Wiesje M. [5 ,10 ]
Lemstra, Afina W. [5 ]
Teunissen, Charlotte E. [1 ,2 ]
机构
[1] Univ Amsterdam, Locat VUmc, Neurochem Lab, Med Ctr,Dept Clin Chem,Amsterdam Neurosci, Amsterdam, Netherlands
[2] Univ Amsterdam, Locat VUmc, Biobank, Med Ctr,Dept Clin Chem,Amsterdam Neurosci, Amsterdam, Netherlands
[3] Pasqual Maragall Fdn, Barcelonabeta Brain Res Ctr, Barcelona, Spain
[4] CEU Univ, Univ San Pablo CEU, Fac Farm, Dept Ciencias Farmaceut & Salud, Madrid, Spain
[5] Univ Amsterdam, Locat VUmc, Alzheimer Ctr Amsterdam, Med Ctr,Dept Neurol,Amsterdam Neurosci, Amsterdam, Netherlands
[6] Wageningen Univ & Res, Math & Stat Methods Grp Biometris, Wageningen, Netherlands
[7] Antwerp Univ, Inst Born Bunge, Neuropathol Lab, Neurobiobank, Edegem, Belgium
[8] Univ Autonoma Barcelona, Hosp St Pau, Inst Invest Biomed St Pau, Dept Neurol,Hosp Santa Creu & St Pau, Barcelona, Catalunya, Spain
[9] Ctr Biomed Invest Network Neurodegenerat Dis CIBE, Madrid, Spain
[10] Univ Amsterdam, Amsterdam Publ Hlth Res Inst, Dept Epidemiol & Data Sci, Locat VUmc,Med Ctr, Amsterdam, Netherlands
[11] Univ Antwerp, Inst Born Bunge, Lab Neurochem & Behav, Reference Ctr Biol Markers Dementia BIODEM, Antwerp, Belgium
[12] Vrije Univ Brussel, Neuroprotect & Neuromodulat Res Grp NEUR, Ctr Neurosci C4N, Brussels, Belgium
[13] Univ Ziekenhuis Brussel, Dept Neurol, Brussels, Belgium
[14] Univ Penn, Perelman Sch Med, Dept Neurol, Philadelphia, PA USA
关键词
MILD COGNITIVE IMPAIRMENT; CEREBROSPINAL-FLUID; ALPHA-SYNUCLEIN; NATIONAL INSTITUTE; ASSOCIATION WORKGROUPS; DIAGNOSTIC GUIDELINES; BETA; 1-42; TAU; RECOMMENDATIONS; MANAGEMENT;
D O I
10.1038/s41467-023-41122-y
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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), Alzheimers 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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页数:14
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