Amyloid, p-tau, neurofilament light, and α-synuclein cerebrospinal fluid biomarkers across Alzheimer's disease, dementia with Lewy bodies, and Parkinson's disease.

IF 4.4 Q1 CLINICAL NEUROLOGY

Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring Pub Date : 2026-10-06 eCollection Date: 2026-10-01 DOI:10.1002/dad2.70498

Marianna Rizzo, Charlotte E Teunissen, Henrik Zetterberg, Kaj Blennow, Gwendlyn Kollmorgen, Rejko Krüger, Sara B G Fernandes, Dag Aarsland, Olga Borejko, Michele Hu, Davit Chokoshvili, Jort E G B Vijverberg, Afina W Lemstra, Betty M Tijms, Gabor C Petzold, Kathrin Brockmann, Thomas Gasser, Giovanni B Frisoni, Jakub Hort, Zuzana Nedelska, Ann-Cecilie Hopøy, Tormod Fladby, Frank Jessen, Emrah Düzel, Annika Spottke, Günter U Höglinger, Sophie Mutel, Claire Chevalier, Rajaraman Krishnan, Pieter Jelle Visser, Stephanie J B Vos

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引用次数: 0

Abstract

Introduction: Mounting evidence suggests overlapping pathology across Alzheimer's disease (AD), dementia with Lewy bodies (DLB), and Parkinson's disease (PD), yet its extent and clinical implications remain unclear.

Methods: Cerebrospinal fluid (CSF) amyloid beta (Aβ)42/40, phosphorylated tau 181 (p-tau181), neurofilament light chain (NfL), and total α-synuclein were centrally measured using fully-automated Elecsys immunoassays in 347 participants (European Platform for Neurodegenerative Diseases [EPND] cohort) and compared between groups. Associations of amyloid and tau positivity with cognitive and motor function were evaluated.

Results: Compared to controls, amyloid and tau levels were abnormal in DLB, but not in PD. Amyloid and tau positivity in DLB were associated with worse global cognitive outcomes, but not with motor performance. NfL levels were elevated across diseases, and total α-synuclein levels were associated with tau positivity.

Discussion: AD pathology is observed in DLB, and related to worse cognition, but it is less observed in PD. CSF NfL captures non-disease-specific processes, whereas CSF total α-synuclein likely reflects CSF tau positivity. Results can help patient management in clinical practice and trials.

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阿尔茨海默病、路易体痴呆和帕金森病的淀粉样蛋白、p-tau、神经丝光和α-突触核蛋白脑脊液生物标志物。

越来越多的证据表明阿尔茨海默病（AD）、路易体痴呆（DLB）和帕金森病（PD）的病理重叠，但其范围和临床意义尚不清楚。方法：采用全自动Elecsys免疫分析法，对347名参与者（欧洲神经退行性疾病平台[EPND]队列）的脑脊液（CSF）淀粉样蛋白β (Aβ)42/40、磷酸化tau181 （p-tau181）、神经丝轻链（NfL）和总α-突触核蛋白进行集中检测，并进行组间比较。评估了淀粉样蛋白和tau蛋白阳性与认知和运动功能的关系。结果：与对照组相比，DLB中淀粉样蛋白和tau蛋白水平异常，而PD中无异常。DLB的淀粉样蛋白和tau蛋白阳性与较差的整体认知结果相关，但与运动表现无关。NfL水平在疾病中升高，α-突触核蛋白总水平与tau阳性相关。讨论：AD病理可在DLB中观察到，并与较差的认知有关，但在PD中较少观察到。CSF NfL捕获非疾病特异性过程，而CSF总α-突触核蛋白可能反映CSF tau阳性。结果可为临床实践和试验中的患者管理提供参考。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring Medicine-Psychiatry and Mental Health

CiteScore

7.80

自引率

7.50%

发文量

101

审稿时长

8 weeks

期刊介绍： Alzheimer''s & Dementia: Diagnosis, Assessment & Disease Monitoring (DADM) is an open access, peer-reviewed, journal from the Alzheimer''s Association® that will publish new research that reports the discovery, development and validation of instruments, technologies, algorithms, and innovative processes. Papers will cover a range of topics interested in the early and accurate detection of individuals with memory complaints and/or among asymptomatic individuals at elevated risk for various forms of memory disorders. The expectation for published papers will be to translate fundamental knowledge about the neurobiology of the disease into practical reports that describe both the conceptual and methodological aspects of the submitted scientific inquiry. Published topics will explore the development of biomarkers, surrogate markers, and conceptual/methodological challenges. Publication priority will be given to papers that 1) describe putative surrogate markers that accurately track disease progression, 2) biomarkers that fulfill international regulatory requirements, 3) reports from large, well-characterized population-based cohorts that comprise the heterogeneity and diversity of asymptomatic individuals and 4) algorithmic development that considers multi-marker arrays (e.g., integrated-omics, genetics, biofluids, imaging, etc.) and advanced computational analytics and technologies.