Unravelling the plasma proteome: Pioneering biomarkers for differential dementia diagnosis

IF 13 1区医学 Q1 CLINICAL NEUROLOGY

Alzheimer's & Dementia Pub Date : 2025-07-04 DOI:10.1002/alz.70162

Haşim Gezegen, Merve Alaylıoğlu, Erdi Şahin, Owen Swann, Elena Veleva, Gamze Güven, Umran Yaman, Derviş A. Salih, Başar Bilgiç, Haşmet Hanağası, Hakan Gürvit, Murat Emre, Duygu Gezen-Ak, Erdinç Dursun, Henrik Zetterberg, John Hardy, Amanda Heslegrave, Maryam Shoai, Bedia Samanci

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引用次数: 0

Abstract

INTRODUCTION

Diagnosing Alzheimer's disease (AD) is challenging due to overlapping symptoms with other dementias and the invasiveness of current biomarkers. This study introduces the NULISA platform, a novel proteomics technology, to evaluate diagnostic accuracy of known biomarkers and uncover novel biomarkers underlying different dementias.

METHODS

We analyzed plasma and cerebrospinal fluid (CSF) samples from 248 participants diagnosed with Alzheimer's disease (AD), dementia with Lewy bodies (DLB), frontotemporal dementia (FTD), and mild cognitive impairment (MCI). Plasma biomarkers were evaluated using regression models, receiver operating characteristics curve (ROC) analysis, and pathway enrichment.

RESULTS

Plasma phosphorylated Tau217 (pTau217) demonstrated the highest diagnostic accuracy for AD, DLB, and FTD (area under the curve [AUCs]: 0.9, 0.84, and 0.79, respectively). CXCL1 (fractalkine), synaptosomal-associated protein 25 (SNAP25), triggering receptor expressed on myeloid cells 1 (TREM1), β-synuclein, and tyrosine kinase (TEK) are expressed differently in DLB and FTD than AD. Ingenuity pathway analyses revealed astrocytic, synaptic, and inflammatory pathways as shared and distinct mechanisms across these dementia types.

CONCLUSION

Our findings establish plasma pTau217 as a robust diagnostic marker. This study provides new plasma biomarkers for differential diagnosis of dementias with a noninvasive method.

Highlights

Plasma pTau217 showed high diagnostic accuracy for AD, DLB, and FTD.
CXCL1, SNAP25, TREM1, β-synuclein, and TEK are novel markers distinguishing other dementias from AD.
Noninvasive plasma biomarkers enable diagnosis and differentiation of dementias.

Abstract Image

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揭示血浆蛋白质组：痴呆鉴别诊断的先锋生物标志物

由于阿尔茨海默病（AD）与其他痴呆症的症状重叠，以及当前生物标志物的侵袭性，诊断阿尔茨海默病（AD）具有挑战性。本研究引入了一种新的蛋白质组学技术NULISA平台，以评估已知生物标志物的诊断准确性，并揭示不同痴呆症的新生物标志物。方法：我们分析了248名被诊断为阿尔茨海默病（AD）、路易体痴呆（DLB）、额颞叶痴呆（FTD）和轻度认知障碍（MCI）的参与者的血浆和脑脊液（CSF）样本。使用回归模型、受试者工作特征曲线（ROC）分析和途径富集来评估血浆生物标志物。结果血浆磷酸化Tau217 （pTau217）对AD、DLB和FTD的诊断准确率最高（曲线下面积[auc]分别为0.9、0.84和0.79）。CXCL1 （fractalkine）、synaptosomal-associated protein 25 （SNAP25）、髓样细胞上表达的触发受体1 （TREM1）、β-synuclein和酪氨酸激酶（TEK）在DLB和FTD中的表达与AD不同。匠心途径分析显示，星形细胞、突触和炎症途径在这些痴呆类型中具有共同和独特的机制。结论血浆pTau217是一种可靠的诊断标志物。本研究为痴呆的无创鉴别诊断提供了新的血浆生物标志物。血浆pTau217对AD、DLB和FTD具有较高的诊断准确性。CXCL1、SNAP25、TREM1、β-synuclein和TEK是区分其他痴呆症和AD的新标志物。无创血浆生物标志物有助于痴呆的诊断和鉴别。

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来源期刊

Alzheimer's & Dementia 医学-临床神经学

CiteScore

14.50

自引率

5.00%

发文量

299

审稿时长

3 months

期刊介绍： Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.