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.
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.
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.