CSF proteome profiling reveals biomarkers to discriminate dementia with Lewy bodies from Alzheimer´s disease
Selected publication · Nature Communications, 2023
del Campo M., Vermunt L., Peeters C., Sieben A., Hok-A-Hin Y., Lleó A., Alcolea D., van Nee M., Engelborghs S., van Alphen J., Arezoumandan S., Chen-Plotkin A., Irwin D., van der Flier W., Lemstra A., Teunissen C.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Neurology | Patient Stratification | CSF | O Olink Target 96 O Olink Focus |
Editor's note
A group led by Charlotte Teunissen at UMC Amsterdam took advantage of the scalability of PEA technology to develop and validate a protein signature that accurately identifies patients with dementia with Lewy bodies (DLB) and discriminates them from cases of Alzheimer’s Disease (AD). The discovery phase used multiple Olink Target 96 panels to measure 665 proteins in cerebrospinal fluid from LBD, identifying multiple DLB-associated markers and deriving a highly accurate, 7-protein signature to discriminate DLB from AD. A custom PEA panel was then developed, enabling the validation of a final 6-protein signature in multiple independent cohorts that discriminated DLB vs AD with an area under the curve (AUC) value of 0.90.
The authors pointed out the advantage of being able to progress through the biomarker discovery, development and validation process without having to change technology platforms at any stage: “We here employed a high-throughput proteomics method, PEA, that allows analysis of large cohorts, with the additional advantage that custom multiplex immunoassays including the markers of interest can be smoothly developed for large-scale validation”.
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.