Aβ status assessment in a hypothetical scenario prior to treatment with disease-modifying therapies: Evidence from 10-year real-world experience at university memory clinics.

IF 4 Q1 CLINICAL NEUROLOGY
Matthias Brendel, Tandis Parvizi, Johannes Gnörich, Christof Elias Topfstedt, Katharina Buerger, Daniel Janowitz, Boris-Stephan Rauchmann, Robert Perneczky, Carolin Kurz, Dirk Mehrens, Wolfgang G Kunz, Julia Kusche-Palenga, Agnes Bernadette Kling, Antonia Buchal, Elizabet Nestorova, Sara Silvaieh, Raphael Wurm, Tatjana Traub-Weidinger, Sigrid Klotz, Günther Regelsberger, Axel Rominger, Alexander Drzezga, Johannes Levin, Elisabeth Stögmann, Nicolai Franzmeier, Günter U Höglinger
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引用次数: 0

Abstract

Introduction: With the advent of disease-modifying therapies, accurate assessment of biomarkers indicating the presence of disease-associated amyloid beta (Aβ) pathology becomes crucial in patients with clinically suspected Alzheimer's disease (AD). We evaluated Aβ levels in cerebrospinal fluid (Aβ CSF) and Aβ levels in positron emission tomography (Aβ PET) biomarkers in a real-world memory-clinic setting to develop an efficient algorithm for clinical use.

Methods: Patients were evaluated for AD-related Aβ pathology from two independent cohorts (Ludwig Maximilian University [LMU], n = 402, and Medical University of Vienna [MUV], n = 144). Optimal thresholds of CSF biomarkers were deduced from receiver operating characteristic curves and validated against Aβ PET positivity.

Results: In both cohorts, a CSF Aβ42/40 ratio ≥ 7.1% was associated with a low risk of a positive Aβ PET scan (negative predictive value: 94.3%). Implementing two cutoffs revealed 14% to 16% of patients with intermediate results (CSF Aβ42/40 ratio: 5.5%-7.1%), which had a strong benefit from Aβ PET imaging (44%-52% Aβ PET positivity).

Discussion: A two-cutoff approach for CSF Aβ42/40 including Aβ PET imaging at intermediate results provides an effective assessment of Aβ pathology in real-world settings.

Highlights: We evaluated cerebrospinal fluid (CSF) and positron emission tomography (PET) amyloid beta (Aβ) biomarkers for Alzheimer's disease in real-world cohorts.A CSF Aβ 42/40 ratio between 5.5% and 7.1% defines patients at borderline levels.Patients at borderline levels strongly benefit from additional Aβ PET imaging.Two-cutoff CSF Aβ 42/40 and PET will allow effective treatment stratification.

在使用疾病改变疗法进行治疗之前,在假设情况下进行 Aβ 状态评估:来自大学记忆诊所 10 年实际经验的证据。
简介随着改变病情疗法的出现,准确评估表明存在与疾病相关的淀粉样蛋白β(Aβ)病理变化的生物标志物对临床疑似阿尔茨海默病(AD)患者至关重要。我们在真实世界的记忆诊所环境中评估了脑脊液(Aβ CSF)中的 Aβ 水平和正电子发射断层扫描(Aβ PET)生物标志物中的 Aβ 水平,以开发出临床使用的有效算法:方法:对两个独立队列(路德维希-马克西米利安大学[Ludwig Maximilian University],n = 402;维也纳医科大学[Medical University of Vienna],n = 144)的患者进行AD相关Aβ病理学评估。根据接收者操作特征曲线推断出脑脊液生物标志物的最佳阈值,并与 Aβ PET 阳性进行了验证:在两个队列中,CSF Aβ42/40 比率≥ 7.1%与 Aβ PET 扫描阳性的低风险相关(阴性预测值:94.3%)。采用两个临界值后,发现14%至16%的患者结果处于中间水平(CSF Aβ42/40比值:5.5%-7.1%),这些患者从Aβ PET成像中获益匪浅(Aβ PET阳性率为44%-52%):讨论:对脑脊液 Aβ42/40 采用两种截断方法,包括中间结果的 Aβ PET 成像,可在实际环境中有效评估 Aβ 病理学:我们评估了现实世界队列中阿尔茨海默病的脑脊液(CSF)和正电子发射断层扫描(PET)淀粉样β(Aβ)生物标记物。
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来源期刊
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.
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