Scholarlink

Background <p>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.</p> Methods <p>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.</p> Results <p>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 <i>p</i> &lt; 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 <i>p</i> &lt; 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 <i>p</i> &lt; 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 <i>p</i> &lt; 0.05).</p> Conclusions <p>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.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Analytical and clinical validation of a novel proximity extension assay-based plasma biomarker panel in a cohort of prevalent neurodegenerative dementias

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月11日

查看全文
  • Giuseppe Mario Bentivenga,
  • Angela Mammana,
  • Simone Baiardi,
  • Erica Vittoriosi,
  • Andrea Mastrangelo,
  • Edoardo Ruggeri,
  • Claudia Marina Vargiu,
  • Barbara Polischi,
  • Michelangelo Stanzani-Maserati,
  • Giovanni Rizzo,
  • Roberta Pantieri,
  • Alberto Raggi,
  • Sabina Capellari,
  • Piero Parchi

摘要

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.