Multiplex plasma proteomics panel achieves high diagnostic accuracy for neurodegenerative dementias
Investigators retrospectively validated the analytical and clinical performance of the Olink Target 48 Neurodegeneration proximity extension assay panel in plasma from 238 patients with diverse neurodegenerative dementias and 65 healthy controls. The platform successfully quantified 32 proteins, with plasma pTau217 demonstrating an area under the curve exceeding 0.91 for Alzheimer disease diagnosis, while novel NEFL-based ratios achieved diagnostic accuracy above 0.93. Thirteen proteins showed significant independent associations with clinical disease staging, and specific markers correlated with Alzheimer and Lewy body pathologies. These findings support the multiplex plasma panel as a minimally invasive alternative to cerebrospinal fluid testing, offering laboratories a validated tool for dementia diagnosis, differential classification, and disease monitoring pending prospective clinical implementation studies.
The original study
Analytical and clinical validation of a novel proximity extension assay-based plasma biomarker panel in a cohort of prevalent neurodegenerative dementias.
- Authors
- Bentivenga GM, Mammana A, Baiardi S, Vittoriosi E, Mastrangelo A, Ruggeri E, et al.
- Journal
- Alzheimer's research & therapy
- Type
- Journal Article
- PMID
- 42436533
Original abstract
BACKGROUND: Blood-based biomarkers are increasingly recognized as promising tools for the diagnosis and monitoring of neurodegenerative diseases, offering a minimally invasive alternative to cerebrospinal fluid (CSF) testing. We evaluated the analytical performance and clinical utility of the Olink Target 48 Neurodegeneration panel, a novel multiplex proteomic platform based on the proximity extension assay (PEA) technology, in a large, clinically diverse dementia cohort. METHODS: We retrospectively analyzed plasma samples from 238 patients with Alzheimer's disease (AD), dementia with Lewy bodies, frontotemporal dementia, progressive supranuclear palsy, and corticobasal degeneration, along with 65 healthy controls, quantifying 41 proteins in each sample. We assessed analytical performance using intra- and inter-assay coefficients of variation, evaluated diagnostic accuracy through receiver operating characteristic curve analysis, and investigated associations between biomarker levels, clinical severity measures, and pathology-specific CSF biomarkers for AD and Lewy body pathology (LBP) using general linear models. RESULTS: The platform quantified 32 proteins with variable analytical performance; nine were excluded due to poor detectability. Strong correlations were observed between PEA-based measurements and established immunoassays for plasma pTau217, NEFL, and GFAP (all p < 0.001). Plasma pTau217 demonstrated superior diagnostic accuracy for AD, achieving an area under the curve (AUC) exceeding 0.91 against all comparison groups. Novel ratios combining NEFL with markers of immune function or synaptic integrity (NEFL/ITGB2, NEFL/ITGAM, NEFL/SCG2) achieved AUCs exceeding 0.93 for discriminating patients from controls, significantly outperforming NEFL alone (all p < 0.001). Thirteen proteins, spanning markers of neuroaxonal damage, myelin-associated processes, and immune function (i.e., Abeta40, Abeta42, BMP7, CLSTN3, ENO2, KLK8, MMP10, NEFL, NPTXR, OMG, RTN4R, SCG2, SDC4, all p < 0.01) showed significant independent associations with disease stage as measured by the Clinical Dementia Rating scale. Four proteins (i.e., pTau217, GFAP, SYT1, and SDC4) were significantly associated with AD pathology, while three (ENO2, ITGAM, and ITGB2) showed significant associations with LBP (all p < 0.05). CONCLUSIONS: This multiplex platform provides multiplex biomarker measurements with potential utility for AD diagnosis and disease staging across neurodegenerative disorders. These findings support further validation studies for its implementation in clinical and research settings.