Methodological Issues in the Clinical Validation of Biomarkers for Alzheimer’s Disease: The Paradigmatic Example of CSF
The use of biomarkers is profoundly transforming medical research and practice. Their adoption has triggered major advancements in the field of Alzheimer’s disease (AD) over the past years. For instance, the analysis of the cerebrospinal fluid (CSF) and neuroimaging changes indicative of neuronal lo...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-10-01
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| Series: | Frontiers in Aging Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fnagi.2019.00282/full |
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| author | Marco Canevelli Marco Canevelli Ilaria Bacigalupo Giuseppe Gervasi Eleonora Lacorte Marco Massari Flavia Mayer Nicola Vanacore Matteo Cesari Matteo Cesari |
| author_facet | Marco Canevelli Marco Canevelli Ilaria Bacigalupo Giuseppe Gervasi Eleonora Lacorte Marco Massari Flavia Mayer Nicola Vanacore Matteo Cesari Matteo Cesari |
| author_sort | Marco Canevelli |
| collection | DOAJ |
| description | The use of biomarkers is profoundly transforming medical research and practice. Their adoption has triggered major advancements in the field of Alzheimer’s disease (AD) over the past years. For instance, the analysis of the cerebrospinal fluid (CSF) and neuroimaging changes indicative of neuronal loss and amyloid deposition has led to the understanding that AD is characterized by a long preclinical phase. It is also supporting the transition towards a biology-grounded framework and definition of the disease. Nevertheless, though sufficient evidence exists about the analytical validity (i.e., accuracy, reliability, and reproducibility) of the candidate AD biomarkers, their clinical validity (i.e., how well the test measures the clinical features, and the disease or treatment outcomes) and clinical utility (i.e., if and how the test improves the patient’s outcomes, confirms/changes the diagnosis, identifies at-risk individuals, influences therapeutic choices) have not been fully proven. In the present review, some of the methodological issues and challenges that should be addressed in order to better appreciate the potential benefits and limitations of AD biomarkers are discussed. The ultimate goal is to stimulate a constructive discussion aimed at filling the existing gaps and more precisely defining the directions of future research. Specifically, four main aspects of the clinical validation process are addressed and applied to the most relevant CSF biomarkers: (1) the definition of reference values; (2) the identification of reference standards for the disease of interest (i.e., AD); (3) the inclusion within the diagnostic process; and (4) the statistical process supporting the whole framework. |
| first_indexed | 2024-12-11T11:42:29Z |
| format | Article |
| id | doaj.art-8848e3b130fb4cd99e843255c801d58b |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-12-11T11:42:29Z |
| publishDate | 2019-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-8848e3b130fb4cd99e843255c801d58b2022-12-22T01:08:35ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652019-10-011110.3389/fnagi.2019.00282475262Methodological Issues in the Clinical Validation of Biomarkers for Alzheimer’s Disease: The Paradigmatic Example of CSFMarco Canevelli0Marco Canevelli1Ilaria Bacigalupo2Giuseppe Gervasi3Eleonora Lacorte4Marco Massari5Flavia Mayer6Nicola Vanacore7Matteo Cesari8Matteo Cesari9Department of Human Neuroscience, Sapienza University, Rome, ItalyNational Center for Disease Prevention and Health Promotion, National Institute of Health, Rome, ItalyNational Center for Disease Prevention and Health Promotion, National Institute of Health, Rome, ItalyNational Center for Disease Prevention and Health Promotion, National Institute of Health, Rome, ItalyNational Center for Disease Prevention and Health Promotion, National Institute of Health, Rome, ItalyNational Center for Drug Research and Evaluation, National Institute of Health, Rome, ItalyNational Center for Disease Prevention and Health Promotion, National Institute of Health, Rome, ItalyNational Center for Disease Prevention and Health Promotion, National Institute of Health, Rome, ItalyFondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, ItalyGeriatric Unit, Department of Clinical Sciences and Community Health, University of Milan, Milan, ItalyThe use of biomarkers is profoundly transforming medical research and practice. Their adoption has triggered major advancements in the field of Alzheimer’s disease (AD) over the past years. For instance, the analysis of the cerebrospinal fluid (CSF) and neuroimaging changes indicative of neuronal loss and amyloid deposition has led to the understanding that AD is characterized by a long preclinical phase. It is also supporting the transition towards a biology-grounded framework and definition of the disease. Nevertheless, though sufficient evidence exists about the analytical validity (i.e., accuracy, reliability, and reproducibility) of the candidate AD biomarkers, their clinical validity (i.e., how well the test measures the clinical features, and the disease or treatment outcomes) and clinical utility (i.e., if and how the test improves the patient’s outcomes, confirms/changes the diagnosis, identifies at-risk individuals, influences therapeutic choices) have not been fully proven. In the present review, some of the methodological issues and challenges that should be addressed in order to better appreciate the potential benefits and limitations of AD biomarkers are discussed. The ultimate goal is to stimulate a constructive discussion aimed at filling the existing gaps and more precisely defining the directions of future research. Specifically, four main aspects of the clinical validation process are addressed and applied to the most relevant CSF biomarkers: (1) the definition of reference values; (2) the identification of reference standards for the disease of interest (i.e., AD); (3) the inclusion within the diagnostic process; and (4) the statistical process supporting the whole framework.https://www.frontiersin.org/article/10.3389/fnagi.2019.00282/fullbiomarkersAlzheimer’s diseasevalidationdiagnostic researchepidemiologymild cognitive impairment |
| spellingShingle | Marco Canevelli Marco Canevelli Ilaria Bacigalupo Giuseppe Gervasi Eleonora Lacorte Marco Massari Flavia Mayer Nicola Vanacore Matteo Cesari Matteo Cesari Methodological Issues in the Clinical Validation of Biomarkers for Alzheimer’s Disease: The Paradigmatic Example of CSF Frontiers in Aging Neuroscience biomarkers Alzheimer’s disease validation diagnostic research epidemiology mild cognitive impairment |
| title | Methodological Issues in the Clinical Validation of Biomarkers for Alzheimer’s Disease: The Paradigmatic Example of CSF |
| title_full | Methodological Issues in the Clinical Validation of Biomarkers for Alzheimer’s Disease: The Paradigmatic Example of CSF |
| title_fullStr | Methodological Issues in the Clinical Validation of Biomarkers for Alzheimer’s Disease: The Paradigmatic Example of CSF |
| title_full_unstemmed | Methodological Issues in the Clinical Validation of Biomarkers for Alzheimer’s Disease: The Paradigmatic Example of CSF |
| title_short | Methodological Issues in the Clinical Validation of Biomarkers for Alzheimer’s Disease: The Paradigmatic Example of CSF |
| title_sort | methodological issues in the clinical validation of biomarkers for alzheimer s disease the paradigmatic example of csf |
| topic | biomarkers Alzheimer’s disease validation diagnostic research epidemiology mild cognitive impairment |
| url | https://www.frontiersin.org/article/10.3389/fnagi.2019.00282/full |
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