Cerebrospinal Fluid Biomarkers in Cerebral Amyloid Angiopathy: New Data and Quantitative Meta-Analysis

To evaluate the diagnostic accuracy of cerebrospinal fluid (CSF) biomarkers in patients with probable cerebral amyloid angiopathy (CAA) according to the modified Boston criteria in a retrospective multicentric cohort. Beta-amyloid 1-40 (Aβ40), beta-amyloid 1-42 (Aβ42), total tau (t-tau), and phospho...

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Published inFrontiers in aging neuroscience Vol. 14; p. 783996
Main Authors Margraf, Nils G., Jensen-Kondering, Ulf, Weiler, Caroline, Leypoldt, Frank, Maetzler, Walter, Philippen, Sarah, Bartsch, Thorsten, Flüh, Charlotte, Röcken, Christoph, Möller, Bettina, Royl, Georg, Neumann, Alexander, Brüggemann, Norbert, Roeben, Benjamin, Schulte, Claudia, Bender, Benjamin, Berg, Daniela, Kuhlenbäumer, Gregor
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Research Foundation 14.02.2022
Frontiers Media S.A
Subjects
Alzheimer's disease
Alzheimer’s dementia (AD)
Automation
Biobanks
Biomarkers
Boston criteria
Cerebral amyloid angiopathy
cerebral amyloid angiopathy (CAA)
Cerebrospinal fluid
cerebrospinal fluid (CSF)
Clinical trials
Dementia
Diagnostic tests
high-precision electro-chemiluminescence immunoassay (ECLIA)
Hospitals
Laboratories
Meta-analysis
Nervous system
Neurodegenerative diseases
Neurological disorders
Neuroscience
Patients
Tau protein
cerebral amyloid angiopathy (CAA)
Boston criteria
cerebrospinal fluid (CSF)
high-precision electro-chemiluminescence immunoassay (ECLIA)
Alzheimer’s dementia (AD)
Online AccessGet full text
ISSN1663-4365
1663-4365
DOI10.3389/fnagi.2022.783996

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Abstract To evaluate the diagnostic accuracy of cerebrospinal fluid (CSF) biomarkers in patients with probable cerebral amyloid angiopathy (CAA) according to the modified Boston criteria in a retrospective multicentric cohort. Beta-amyloid 1-40 (Aβ40), beta-amyloid 1-42 (Aβ42), total tau (t-tau), and phosphorylated tau 181 (p-tau ) were measured in 31 patients with probable CAA, 28 patients with Alzheimer's disease (AD), and 30 controls. Receiver-operating characteristics (ROC) analyses were performed for the measured parameters as well as the Aβ42/40 ratio to estimate diagnostic parameters. A meta-analysis of all amenable published studies was conducted. In our data Aβ42/40 (AUC 0.88) discriminated best between CAA and controls while Aβ40 did not perform well (AUC 0.63). Differentiating between CAA and AD, p-tau (AUC 0.75) discriminated best in this study while Aβ40 (AUC 0.58) and Aβ42 (AUC 0.54) provided no discrimination. In the meta-analysis, Aβ42/40 (AUC 0.90) showed the best discrimination between CAA and controls followed by t-tau (AUC 0.79), Aβ40 (AUC 0.76), and p-tau (AUC 0.71). P-tau (AUC 0.76), Aβ40 (AUC 0.73), and t-tau (AUC 0.71) differentiated comparably between AD and CAA while Aβ42 (AUC 0.54) did not. In agreement with studies examining AD biomarkers, Aβ42/40 discriminated excellently between AD and controls (AUC 0.92-0.96) in this study as well as the meta-analysis. The analyzed parameters differentiate between controls and CAA with clinically useful accuracy (AUC > ∼0.85) but not between CAA and AD. Since there is a neuropathological, clinical and diagnostic continuum between CAA and AD, other diagnostic markers, e.g., novel CSF biomarkers or other parameters might be more successful.
AbstractList Background: To evaluate the diagnostic accuracy of CSF biomarkers in patients with probable cerebral amyloid angiopathy (CAA) according to the Modified Boston criteria in a retrospective multicentric cohort. Methods: Aß40, Aß42, t-tau, and p-tau181 were measured in 31 patients with probable CAA, 28 patients with Alzheimer’s disease (AD), and 30 controls. Receiver-operating characteristics (ROC) analyses were performed for the measured parameters as well as the Aß42/40 ratio to estimate diagnostic parameters. A meta-analysis of all amenable published studies was conducted. Results: In our data Aß42/40 (AUC 0.88) discriminated best between CAA and controls while Aß40 did not perform well (AUC 0.63). Differentiating between CAA and AD, p-tau181 (AUC 0.75) discriminated best in this study while Aß40 (AUC 0.58) and Aß42 (AUC 0.54) provided no discrimination. In the meta-analysis, Aß42/40 (AUC 0.90) showed the best discrimination between CAA and controls followed by t-tau (AUC 0.79), Aß40 (AUC 0.76), and p-tau181 (AUC 0.71). p-tau181 (AUC 0.76), Aß40 (AUC 0.73), and t-tau (AUC 0.71) differentiated comparably between AD and CAA while Aß42 (AUC 0.54) did not. In agreement with studies examining AD biomarkers, Aß42/40 discriminated excellently between AD and controls (AUC 0.92-0.96) in this study as well as the meta-analysis. Conclusions: The analyzed parameters differentiate between controls and CAA with clinically useful accuracy (AUC > ~ 0.85) but not between CAA and AD. Since there is a neuropathological, clinical and diagnostic continuum between CAA and AD, other diagnostic markers, e.g. novel CSF biomarkers or other parameters might be more successful.
To evaluate the diagnostic accuracy of cerebrospinal fluid (CSF) biomarkers in patients with probable cerebral amyloid angiopathy (CAA) according to the modified Boston criteria in a retrospective multicentric cohort.BACKGROUNDTo evaluate the diagnostic accuracy of cerebrospinal fluid (CSF) biomarkers in patients with probable cerebral amyloid angiopathy (CAA) according to the modified Boston criteria in a retrospective multicentric cohort.Beta-amyloid 1-40 (Aβ40), beta-amyloid 1-42 (Aβ42), total tau (t-tau), and phosphorylated tau 181 (p-tau181) were measured in 31 patients with probable CAA, 28 patients with Alzheimer's disease (AD), and 30 controls. Receiver-operating characteristics (ROC) analyses were performed for the measured parameters as well as the Aβ42/40 ratio to estimate diagnostic parameters. A meta-analysis of all amenable published studies was conducted.METHODSBeta-amyloid 1-40 (Aβ40), beta-amyloid 1-42 (Aβ42), total tau (t-tau), and phosphorylated tau 181 (p-tau181) were measured in 31 patients with probable CAA, 28 patients with Alzheimer's disease (AD), and 30 controls. Receiver-operating characteristics (ROC) analyses were performed for the measured parameters as well as the Aβ42/40 ratio to estimate diagnostic parameters. A meta-analysis of all amenable published studies was conducted.In our data Aβ42/40 (AUC 0.88) discriminated best between CAA and controls while Aβ40 did not perform well (AUC 0.63). Differentiating between CAA and AD, p-tau181 (AUC 0.75) discriminated best in this study while Aβ40 (AUC 0.58) and Aβ42 (AUC 0.54) provided no discrimination. In the meta-analysis, Aβ42/40 (AUC 0.90) showed the best discrimination between CAA and controls followed by t-tau (AUC 0.79), Aβ40 (AUC 0.76), and p-tau181 (AUC 0.71). P-tau181 (AUC 0.76), Aβ40 (AUC 0.73), and t-tau (AUC 0.71) differentiated comparably between AD and CAA while Aβ42 (AUC 0.54) did not. In agreement with studies examining AD biomarkers, Aβ42/40 discriminated excellently between AD and controls (AUC 0.92-0.96) in this study as well as the meta-analysis.RESULTSIn our data Aβ42/40 (AUC 0.88) discriminated best between CAA and controls while Aβ40 did not perform well (AUC 0.63). Differentiating between CAA and AD, p-tau181 (AUC 0.75) discriminated best in this study while Aβ40 (AUC 0.58) and Aβ42 (AUC 0.54) provided no discrimination. In the meta-analysis, Aβ42/40 (AUC 0.90) showed the best discrimination between CAA and controls followed by t-tau (AUC 0.79), Aβ40 (AUC 0.76), and p-tau181 (AUC 0.71). P-tau181 (AUC 0.76), Aβ40 (AUC 0.73), and t-tau (AUC 0.71) differentiated comparably between AD and CAA while Aβ42 (AUC 0.54) did not. In agreement with studies examining AD biomarkers, Aβ42/40 discriminated excellently between AD and controls (AUC 0.92-0.96) in this study as well as the meta-analysis.The analyzed parameters differentiate between controls and CAA with clinically useful accuracy (AUC > ∼0.85) but not between CAA and AD. Since there is a neuropathological, clinical and diagnostic continuum between CAA and AD, other diagnostic markers, e.g., novel CSF biomarkers or other parameters might be more successful.CONCLUSIONThe analyzed parameters differentiate between controls and CAA with clinically useful accuracy (AUC > ∼0.85) but not between CAA and AD. Since there is a neuropathological, clinical and diagnostic continuum between CAA and AD, other diagnostic markers, e.g., novel CSF biomarkers or other parameters might be more successful.
To evaluate the diagnostic accuracy of cerebrospinal fluid (CSF) biomarkers in patients with probable cerebral amyloid angiopathy (CAA) according to the modified Boston criteria in a retrospective multicentric cohort. Beta-amyloid 1-40 (Aβ40), beta-amyloid 1-42 (Aβ42), total tau (t-tau), and phosphorylated tau 181 (p-tau ) were measured in 31 patients with probable CAA, 28 patients with Alzheimer's disease (AD), and 30 controls. Receiver-operating characteristics (ROC) analyses were performed for the measured parameters as well as the Aβ42/40 ratio to estimate diagnostic parameters. A meta-analysis of all amenable published studies was conducted. In our data Aβ42/40 (AUC 0.88) discriminated best between CAA and controls while Aβ40 did not perform well (AUC 0.63). Differentiating between CAA and AD, p-tau (AUC 0.75) discriminated best in this study while Aβ40 (AUC 0.58) and Aβ42 (AUC 0.54) provided no discrimination. In the meta-analysis, Aβ42/40 (AUC 0.90) showed the best discrimination between CAA and controls followed by t-tau (AUC 0.79), Aβ40 (AUC 0.76), and p-tau (AUC 0.71). P-tau (AUC 0.76), Aβ40 (AUC 0.73), and t-tau (AUC 0.71) differentiated comparably between AD and CAA while Aβ42 (AUC 0.54) did not. In agreement with studies examining AD biomarkers, Aβ42/40 discriminated excellently between AD and controls (AUC 0.92-0.96) in this study as well as the meta-analysis. The analyzed parameters differentiate between controls and CAA with clinically useful accuracy (AUC > ∼0.85) but not between CAA and AD. Since there is a neuropathological, clinical and diagnostic continuum between CAA and AD, other diagnostic markers, e.g., novel CSF biomarkers or other parameters might be more successful.
BackgroundTo evaluate the diagnostic accuracy of cerebrospinal fluid (CSF) biomarkers in patients with probable cerebral amyloid angiopathy (CAA) according to the modified Boston criteria in a retrospective multicentric cohort.MethodsBeta-amyloid 1-40 (Aβ40), beta-amyloid 1-42 (Aβ42), total tau (t-tau), and phosphorylated tau 181 (p-tau181) were measured in 31 patients with probable CAA, 28 patients with Alzheimer’s disease (AD), and 30 controls. Receiver-operating characteristics (ROC) analyses were performed for the measured parameters as well as the Aβ42/40 ratio to estimate diagnostic parameters. A meta-analysis of all amenable published studies was conducted.ResultsIn our data Aβ42/40 (AUC 0.88) discriminated best between CAA and controls while Aβ40 did not perform well (AUC 0.63). Differentiating between CAA and AD, p-tau181 (AUC 0.75) discriminated best in this study while Aβ40 (AUC 0.58) and Aβ42 (AUC 0.54) provided no discrimination. In the meta-analysis, Aβ42/40 (AUC 0.90) showed the best discrimination between CAA and controls followed by t-tau (AUC 0.79), Aβ40 (AUC 0.76), and p-tau181 (AUC 0.71). P-tau181 (AUC 0.76), Aβ40 (AUC 0.73), and t-tau (AUC 0.71) differentiated comparably between AD and CAA while Aβ42 (AUC 0.54) did not. In agreement with studies examining AD biomarkers, Aβ42/40 discriminated excellently between AD and controls (AUC 0.92–0.96) in this study as well as the meta-analysis.ConclusionThe analyzed parameters differentiate between controls and CAA with clinically useful accuracy (AUC > ∼0.85) but not between CAA and AD. Since there is a neuropathological, clinical and diagnostic continuum between CAA and AD, other diagnostic markers, e.g., novel CSF biomarkers or other parameters might be more successful.
Author Maetzler, Walter
Berg, Daniela
Kuhlenbäumer, Gregor
Margraf, Nils G.
Jensen-Kondering, Ulf
Flüh, Charlotte
Röcken, Christoph
Roeben, Benjamin
Leypoldt, Frank
Philippen, Sarah
Möller, Bettina
Royl, Georg
Bartsch, Thorsten
Bender, Benjamin
Brüggemann, Norbert
Neumann, Alexander
Schulte, Claudia
Weiler, Caroline
AuthorAffiliation 4 Institute of Clinical Chemistry, University Medical Center Schleswig-Holstein , Kiel/Lübeck , Germany
2 Department of Radiology and Neuroradiology, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel University , Kiel , Germany
3 Department of Neuroradiology, University Medical Center Schleswig-Holstein, Campus Lübeck , Lübeck , Germany
8 Institute of Neurogenetics, University of Lübeck , Lübeck , Germany
5 Department of Neurosurgery, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel University , Kiel , Germany
7 Department of Neurology, University Medical Center Schleswig Holstein, Campus Lübeck , Lübeck , Germany
11 Department of Neuroradiology, Diagnostical and Interventional Neuroradiology, University Hospital of Tübingen , Tübingen , Germany
1 Department of Neurology, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel University , Kiel , Germany
6 Department of Pathology, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel University ,
AuthorAffiliation_xml – name: 5 Department of Neurosurgery, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel University , Kiel , Germany
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/35237145$$D View this record in MEDLINE/PubMed
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ContentType Journal Article
Copyright Copyright © 2022 Margraf, Jensen-Kondering, Weiler, Leypoldt, Maetzler, Philippen, Bartsch, Flüh, Röcken, Möller, Royl, Neumann, Brüggemann, Roeben, Schulte, Bender, Berg and Kuhlenbäumer.
2022. This work is licensed under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
Copyright © 2022 Margraf, Jensen-Kondering, Weiler, Leypoldt, Maetzler, Philippen, Bartsch, Flüh, Röcken, Möller, Royl, Neumann, Brüggemann, Roeben, Schulte, Bender, Berg and Kuhlenbäumer. 2022 Margraf, Jensen-Kondering, Weiler, Leypoldt, Maetzler, Philippen, Bartsch, Flüh, Röcken, Möller, Royl, Neumann, Brüggemann, Roeben, Schulte, Bender, Berg and Kuhlenbäumer
Copyright_xml – notice: Copyright © 2022 Margraf, Jensen-Kondering, Weiler, Leypoldt, Maetzler, Philippen, Bartsch, Flüh, Röcken, Möller, Royl, Neumann, Brüggemann, Roeben, Schulte, Bender, Berg and Kuhlenbäumer.
– notice: 2022. This work is licensed under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
– notice: Copyright © 2022 Margraf, Jensen-Kondering, Weiler, Leypoldt, Maetzler, Philippen, Bartsch, Flüh, Röcken, Möller, Royl, Neumann, Brüggemann, Roeben, Schulte, Bender, Berg and Kuhlenbäumer. 2022 Margraf, Jensen-Kondering, Weiler, Leypoldt, Maetzler, Philippen, Bartsch, Flüh, Röcken, Möller, Royl, Neumann, Brüggemann, Roeben, Schulte, Bender, Berg and Kuhlenbäumer
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Keywords cerebral amyloid angiopathy (CAA)
Boston criteria
cerebrospinal fluid (CSF)
high-precision electro-chemiluminescence immunoassay (ECLIA)
Alzheimer’s dementia (AD)
Language English
License Copyright © 2022 Margraf, Jensen-Kondering, Weiler, Leypoldt, Maetzler, Philippen, Bartsch, Flüh, Röcken, Möller, Royl, Neumann, Brüggemann, Roeben, Schulte, Bender, Berg and Kuhlenbäumer.
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This article was submitted to Alzheimer’s Disease and Related Dementias, a section of the journal Frontiers in Aging Neuroscience
Reviewed by: Mitsuru Shinohara, National Center for Geriatrics and Gerontology (NCGG), Japan; Amy Renee Nelson, University of South Alabama, United States
These authors have contributed equally to this work and share first authorship
Edited by: Jiehui Jiang, Shanghai University, China
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PublicationTitle Frontiers in aging neuroscience
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Snippet To evaluate the diagnostic accuracy of cerebrospinal fluid (CSF) biomarkers in patients with probable cerebral amyloid angiopathy (CAA) according to the...
Background: To evaluate the diagnostic accuracy of CSF biomarkers in patients with probable cerebral amyloid angiopathy (CAA) according to the Modified Boston...
BackgroundTo evaluate the diagnostic accuracy of cerebrospinal fluid (CSF) biomarkers in patients with probable cerebral amyloid angiopathy (CAA) according to...
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SubjectTerms Alzheimer's disease
Alzheimer’s dementia (AD)
Automation
Biobanks
Biomarkers
Boston criteria
Cerebral amyloid angiopathy
cerebral amyloid angiopathy (CAA)
Cerebrospinal fluid
cerebrospinal fluid (CSF)
Clinical trials
Dementia
Diagnostic tests
high-precision electro-chemiluminescence immunoassay (ECLIA)
Hospitals
Laboratories
Meta-analysis
Nervous system
Neurodegenerative diseases
Neurological disorders
Neuroscience
Patients
Tau protein
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Title Cerebrospinal Fluid Biomarkers in Cerebral Amyloid Angiopathy: New Data and Quantitative Meta-Analysis
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