Large‐scale plasma proteomic profiling identifies a high‐performance biomarker panel for Alzheimer's disease screening and staging
Selected publication · Alzheimer's & Dementia, 2021
Jiang Y., Zhou X., Ip F., Chan P., Chen Y., Lai N., Cheung K., Lo R., Tong E., Wong B., Chan A., Mok V., Kwok T., Mok K., Hardy J., Zetterberg H., Fu A., Ip N.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Neurology | Patient Stratification | Plasma |  Olink Target 96 |
Editor's note
PEA technology has been used extensively in the study of Alzheimer’s Disease (AD), with many disease-related proteins identified in the key neurological sample matrix, cerebrospinal fluid (CSF). This has provided many important biological insights and potential new biomarkers for AD, but the collection of CSF is relatively invasive, with potential discomfort and anxiety issues for patients. In this study, the researchers focused on plasma proteomics in order to identify minimally invasive biomarkers for AD research. Consequently, they examined almost 1, 200 proteins in plasma from AD patients and controls using the full range of Olink Target 96 panels, identifying a 19-protein signature that identified clinical AD with very high accuracy. The authors concluded, “Our findings not only serve as a foundation for the development of a high-performance, blood-based test for AD screening and monitoring in clinical settings but also provide abundant protein targets for future therapeutic development”.
Abstract
Introduction
Blood proteins are emerging as candidate biomarkers for Alzheimer’s disease (AD). We systematically profiled the plasma proteome to identify novel AD blood biomarkers and develop a high‐performance, blood‐based test for AD.
Methods
We quantified 1160 plasma proteins in a Hong Kong Chinese cohort by high‐throughput proximity extension assay and validated the results in an independent cohort. In subgroup analyses, plasma biomarkers for amyloid, tau, phosphorylated tau, and neurodegeneration were used as endophenotypes of AD.
Results
We identified 429 proteins that were dysregulated in AD plasma. We selected 19 “hub proteins” representative of the AD plasma protein profile, which formed the basis of a scoring system that accurately classified clinical AD (area under the curve = 0.9690–0.9816) and associated endophenotypes. Moreover, specific hub proteins exhibit disease stage‐dependent dysregulation, which can delineate AD stages.
Discussion
This study comprehensively profiled the AD plasma proteome and serves as a foundation for a high‐performance, blood‐based test for clinical AD screening and staging.