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
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 cerebrospin...
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Wiley
2024-10-01
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| Series: | Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring |
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| Online Access: | https://doi.org/10.1002/dad2.70031 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Matthias Brendel |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-7fb30f95958a481fb8b2ea89e020010b |
| institution | DOAJ |
| issn | 2352-8729 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | Wiley |
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| series | Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring |
| spelling | doaj-art-7fb30f95958a481fb8b2ea89e020010b2025-08-20T02:55:53ZengWileyAlzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring2352-87292024-10-01164n/an/a10.1002/dad2.70031Aβ status assessment in a hypothetical scenario prior to treatment with disease‐modifying therapies: Evidence from 10‐year real‐world experience at university memory clinicsMatthias Brendel0Tandis Parvizi1Johannes Gnörich2Christof Elias Topfstedt3Katharina Buerger4Daniel Janowitz5Boris‐Stephan Rauchmann6Robert Perneczky7Carolin Kurz8Dirk Mehrens9Wolfgang G. Kunz10Julia Kusche‐Palenga11Agnes Bernadette Kling12Antonia Buchal13Elizabet Nestorova14Sara Silvaieh15Raphael Wurm16Tatjana Traub‐Weidinger17Sigrid Klotz18Günther Regelsberger19Axel Rominger20Alexander Drzezga21Johannes Levin22Elisabeth Stögmann23Nicolai Franzmeier24Günter U. Höglinger25Department of Nuclear MedicineLMU University Hospital, LMU MunichMunich GermanyDepartment of Nuclear MedicineLMU University Hospital, LMU MunichMunich GermanyDepartment of Nuclear MedicineLMU University Hospital, LMU MunichMunich GermanyInstitute for Stroke and Dementia Research (ISD)LMU University Hospital, LMU MunichMunich GermanyGerman Center for Neurodegenerative Diseases (DZNE) MunichMunichGermanyInstitute for Stroke and Dementia Research (ISD)LMU University Hospital, LMU MunichMunich GermanyDepartment of Psychiatry and PsychotherapyLMU University Hospital, LMU MunichMunich GermanyGerman Center for Neurodegenerative Diseases (DZNE) MunichMunichGermanyDepartment of Psychiatry and PsychotherapyLMU University Hospital, LMU MunichMunich GermanyDepartment of RadiologyLMU University Hospital, LMU MunichMunich GermanyDepartment of RadiologyLMU University Hospital, LMU MunichMunich GermanyDepartment of Nuclear MedicineLMU University Hospital, LMU MunichMunich GermanyDepartment of Nuclear MedicineLMU University Hospital, LMU MunichMunich GermanyDepartment of RadiologyLMU University Hospital, LMU MunichMunich GermanyDepartment of Psychiatry and PsychotherapyLMU University Hospital, LMU MunichMunich GermanyDepartment of NeurologyMedical University of ViennaViennaAustriaDepartment of NeurologyMedical University of ViennaViennaAustriaDivision of Nuclear Medicine, Department of Biomedical Imaging and Image‐Guided TherapyMedical University of ViennaViennaAustriaComprehensive Center for Clinical Neurosciences and Mental HealthMedical University of ViennaViennaAustriaComprehensive Center for Clinical Neurosciences and Mental HealthMedical University of ViennaViennaAustriaDepartment of Nuclear Medicine, InselspitalBern University Hospital, University of BernBernSwitzerlandDepartment of Nuclear MedicineFaculty of Medicine and University Hospital CologneCologneGermanyGerman Center for Neurodegenerative Diseases (DZNE) MunichMunichGermanyDepartment of NeurologyMedical University of ViennaViennaAustriaMunich Cluster for Systems Neurology (SyNergy)MunichGermanyGerman Center for Neurodegenerative Diseases (DZNE) MunichMunichGermanyAbstract 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.https://doi.org/10.1002/dad2.70031Alzheimer's diseasebiomarkerscerebrospinal fluiddementiapositron emission tomographyreal world |
| spellingShingle | 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 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 Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring Alzheimer's disease biomarkers cerebrospinal fluid dementia positron emission tomography real world |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | Alzheimer's disease biomarkers cerebrospinal fluid dementia positron emission tomography real world |
| url | https://doi.org/10.1002/dad2.70031 |
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