Biological variation estimates of Alzheimer's disease plasma biomarkers in healthy individuals
INTRODUCTION Blood biomarkers have proven useful in Alzheimer's disease (AD) research. However, little is known about their biological variation (BV), which improves the interpretation of individual‐level data. METHODS We measured plasma amyloid beta (Aβ42, Aβ40), phosphorylated tau (p‐tau181,...
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| Published in | Alzheimer's & dementia Vol. 20; no. 2; pp. 1284 - 1297 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
John Wiley & Sons, Inc
01.02.2024
John Wiley and Sons Inc |
| Subjects | |
| Online Access | Get full text |
| ISSN | 1552-5260 1552-5279 1552-5279 |
| DOI | 10.1002/alz.13518 |
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| Abstract | INTRODUCTION
Blood biomarkers have proven useful in Alzheimer's disease (AD) research. However, little is known about their biological variation (BV), which improves the interpretation of individual‐level data.
METHODS
We measured plasma amyloid beta (Aβ42, Aβ40), phosphorylated tau (p‐tau181, p‐tau217, p‐tau231), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) in plasma samples collected weekly over 10 weeks from 20 participants aged 40 to 60 years from the European Biological Variation Study. We estimated within‐ (CVI) and between‐subject (CVG) BV, analytical variation, and reference change values (RCV).
RESULTS
Biomarkers presented considerable variability in CVI and CVG. Aβ42/Aβ40 had the lowest CVI (≈ 3%) and p‐tau181 the highest (≈ 16%), while others ranged from 6% to 10%. Most RCVs ranged from 20% to 30% (decrease) and 25% to 40% (increase).
DISCUSSION
BV estimates for AD plasma biomarkers can potentially refine their clinical and research interpretation. RCVs might be useful for detecting significant changes between serial measurements when monitoring early disease progression or interventions.
Highlights
Plasma amyloid beta (Aβ42/Aβ40) presents the lowest between‐ and within‐subject biological variation, but also changes the least in Alzheimer's disease (AD) patients versus controls.
Plasma phosphorylated tau variants significantly vary in their within‐subject biological variation, but their substantial fold‐changes in AD likely limits the impact of their variability.
Plasma neurofilament light chain and glial fibrillary acidic protein demonstrate high between‐subject variation, the impact of which will depend on clinical context.
Reference change values can potentially be useful in monitoring early disease progression and the safety/efficacy of interventions on an individual level.
Serial sampling revealed that unexpectedly high values in heathy individuals can be observed, which urges caution when interpreting AD plasma biomarkers based on a single test result. |
|---|---|
| AbstractList | INTRODUCTION Blood biomarkers have proven useful in Alzheimer's disease (AD) research. However, little is known about their biological variation (BV), which improves the interpretation of individual‐level data. METHODS We measured plasma amyloid beta (Aβ42, Aβ40), phosphorylated tau (p‐tau181, p‐tau217, p‐tau231), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) in plasma samples collected weekly over 10 weeks from 20 participants aged 40 to 60 years from the European Biological Variation Study. We estimated within‐ (CVI) and between‐subject (CVG) BV, analytical variation, and reference change values (RCV). RESULTS Biomarkers presented considerable variability in CVI and CVG. Aβ42/Aβ40 had the lowest CVI (≈ 3%) and p‐tau181 the highest (≈ 16%), while others ranged from 6% to 10%. Most RCVs ranged from 20% to 30% (decrease) and 25% to 40% (increase). DISCUSSION BV estimates for AD plasma biomarkers can potentially refine their clinical and research interpretation. RCVs might be useful for detecting significant changes between serial measurements when monitoring early disease progression or interventions. Highlights Plasma amyloid beta (Aβ42/Aβ40) presents the lowest between‐ and within‐subject biological variation, but also changes the least in Alzheimer's disease (AD) patients versus controls. Plasma phosphorylated tau variants significantly vary in their within‐subject biological variation, but their substantial fold‐changes in AD likely limits the impact of their variability. Plasma neurofilament light chain and glial fibrillary acidic protein demonstrate high between‐subject variation, the impact of which will depend on clinical context. Reference change values can potentially be useful in monitoring early disease progression and the safety/efficacy of interventions on an individual level. Serial sampling revealed that unexpectedly high values in heathy individuals can be observed, which urges caution when interpreting AD plasma biomarkers based on a single test result. INTRODUCTION: Blood biomarkers have proven useful in Alzheimer's disease (AD) research. However, little is known about their biological variation (BV), which improves the interpretation of individual-level data. METHODS: We measured plasma amyloid beta (Aβ42, Aβ40), phosphorylated tau (p-tau181, p-tau217, p-tau231), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) in plasma samples collected weekly over 10weeks from 20 participants aged 40 to 60 years from the European Biological Variation Study. We estimated within- (CVI) and between-subject (CVG) BV, analytical variation, and reference change values (RCV). RESULTS: Biomarkers presented considerable variability in CVI and CVG. Aβ42/Aβ40 had the lowest CVI (≈ 3%) and p-tau181 the highest (≈ 16%), while others ranged from 6% to 10%. Most RCVs ranged from 20% to 30% (decrease) and 25% to 40% (increase). DISCUSSION: BV estimates for AD plasma biomarkers can potentially refine their clinical and research interpretation. RCVs might be useful for detecting significant changes between serial measurements when monitoring early disease progression or interventions. Highlights Plasma amyloid beta (Aβ42/Aβ40) presents the lowest between- and within-subject biological variation, but also changes the least in Alzheimer's disease (AD) patients versus controls. Plasma phosphorylated tau variants significantly vary in their within-subject biological variation, but their substantial fold-changes in AD likely limits the impact of their variability. Plasma neurofilament light chain and glial fibrillary acidic protein demonstrate high between-subject variation, the impact of which will depend on clinical context. Reference change values can potentially be useful in monitoring early disease progression and the safety/efficacy of interventions on an individual level. Serial sampling revealed that unexpectedly high values in heathy individuals can be observed, which urges caution when interpreting AD plasma biomarkers based on a single test result. INTRODUCTION Blood biomarkers have proven useful in Alzheimer's disease (AD) research. However, little is known about their biological variation (BV), which improves the interpretation of individual‐level data. METHODS We measured plasma amyloid beta (Aβ42, Aβ40), phosphorylated tau (p‐tau181, p‐tau217, p‐tau231), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) in plasma samples collected weekly over 10 weeks from 20 participants aged 40 to 60 years from the European Biological Variation Study. We estimated within‐ (CVI) and between‐subject (CVG) BV, analytical variation, and reference change values (RCV). RESULTS Biomarkers presented considerable variability in CVI and CVG. Aβ42/Aβ40 had the lowest CVI (≈ 3%) and p‐tau181 the highest (≈ 16%), while others ranged from 6% to 10%. Most RCVs ranged from 20% to 30% (decrease) and 25% to 40% (increase). DISCUSSION BV estimates for AD plasma biomarkers can potentially refine their clinical and research interpretation. RCVs might be useful for detecting significant changes between serial measurements when monitoring early disease progression or interventions. Highlights Plasma amyloid beta (Aβ42/Aβ40) presents the lowest between‐ and within‐subject biological variation, but also changes the least in Alzheimer's disease (AD) patients versus controls. Plasma phosphorylated tau variants significantly vary in their within‐subject biological variation, but their substantial fold‐changes in AD likely limits the impact of their variability. Plasma neurofilament light chain and glial fibrillary acidic protein demonstrate high between‐subject variation, the impact of which will depend on clinical context. Reference change values can potentially be useful in monitoring early disease progression and the safety/efficacy of interventions on an individual level. Serial sampling revealed that unexpectedly high values in heathy individuals can be observed, which urges caution when interpreting AD plasma biomarkers based on a single test result. Blood biomarkers have proven useful in Alzheimer's disease (AD) research. However, little is known about their biological variation (BV), which improves the interpretation of individual-level data. We measured plasma amyloid beta (Aβ42, Aβ40), phosphorylated tau (p-tau181, p-tau217, p-tau231), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) in plasma samples collected weekly over 10 weeks from 20 participants aged 40 to 60 years from the European Biological Variation Study. We estimated within- (CV ) and between-subject (CV ) BV, analytical variation, and reference change values (RCV). Biomarkers presented considerable variability in CV and CV . Aβ42/Aβ40 had the lowest CV (≈ 3%) and p-tau181 the highest (≈ 16%), while others ranged from 6% to 10%. Most RCVs ranged from 20% to 30% (decrease) and 25% to 40% (increase). BV estimates for AD plasma biomarkers can potentially refine their clinical and research interpretation. RCVs might be useful for detecting significant changes between serial measurements when monitoring early disease progression or interventions. Highlights Plasma amyloid beta (Aβ42/Aβ40) presents the lowest between- and within-subject biological variation, but also changes the least in Alzheimer's disease (AD) patients versus controls. Plasma phosphorylated tau variants significantly vary in their within-subject biological variation, but their substantial fold-changes in AD likely limits the impact of their variability. Plasma neurofilament light chain and glial fibrillary acidic protein demonstrate high between-subject variation, the impact of which will depend on clinical context. Reference change values can potentially be useful in monitoring early disease progression and the safety/efficacy of interventions on an individual level. Serial sampling revealed that unexpectedly high values in heathy individuals can be observed, which urges caution when interpreting AD plasma biomarkers based on a single test result. Blood biomarkers have proven useful in Alzheimer's disease (AD) research. However, little is known about their biological variation (BV), which improves the interpretation of individual-level data.INTRODUCTIONBlood biomarkers have proven useful in Alzheimer's disease (AD) research. However, little is known about their biological variation (BV), which improves the interpretation of individual-level data.We measured plasma amyloid beta (Aβ42, Aβ40), phosphorylated tau (p-tau181, p-tau217, p-tau231), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) in plasma samples collected weekly over 10 weeks from 20 participants aged 40 to 60 years from the European Biological Variation Study. We estimated within- (CVI ) and between-subject (CVG ) BV, analytical variation, and reference change values (RCV).METHODSWe measured plasma amyloid beta (Aβ42, Aβ40), phosphorylated tau (p-tau181, p-tau217, p-tau231), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) in plasma samples collected weekly over 10 weeks from 20 participants aged 40 to 60 years from the European Biological Variation Study. We estimated within- (CVI ) and between-subject (CVG ) BV, analytical variation, and reference change values (RCV).Biomarkers presented considerable variability in CVI and CVG . Aβ42/Aβ40 had the lowest CVI (≈ 3%) and p-tau181 the highest (≈ 16%), while others ranged from 6% to 10%. Most RCVs ranged from 20% to 30% (decrease) and 25% to 40% (increase).RESULTSBiomarkers presented considerable variability in CVI and CVG . Aβ42/Aβ40 had the lowest CVI (≈ 3%) and p-tau181 the highest (≈ 16%), while others ranged from 6% to 10%. Most RCVs ranged from 20% to 30% (decrease) and 25% to 40% (increase).BV estimates for AD plasma biomarkers can potentially refine their clinical and research interpretation. RCVs might be useful for detecting significant changes between serial measurements when monitoring early disease progression or interventions. Highlights Plasma amyloid beta (Aβ42/Aβ40) presents the lowest between- and within-subject biological variation, but also changes the least in Alzheimer's disease (AD) patients versus controls. Plasma phosphorylated tau variants significantly vary in their within-subject biological variation, but their substantial fold-changes in AD likely limits the impact of their variability. Plasma neurofilament light chain and glial fibrillary acidic protein demonstrate high between-subject variation, the impact of which will depend on clinical context. Reference change values can potentially be useful in monitoring early disease progression and the safety/efficacy of interventions on an individual level. Serial sampling revealed that unexpectedly high values in heathy individuals can be observed, which urges caution when interpreting AD plasma biomarkers based on a single test result.DISCUSSIONBV estimates for AD plasma biomarkers can potentially refine their clinical and research interpretation. RCVs might be useful for detecting significant changes between serial measurements when monitoring early disease progression or interventions. Highlights Plasma amyloid beta (Aβ42/Aβ40) presents the lowest between- and within-subject biological variation, but also changes the least in Alzheimer's disease (AD) patients versus controls. Plasma phosphorylated tau variants significantly vary in their within-subject biological variation, but their substantial fold-changes in AD likely limits the impact of their variability. Plasma neurofilament light chain and glial fibrillary acidic protein demonstrate high between-subject variation, the impact of which will depend on clinical context. Reference change values can potentially be useful in monitoring early disease progression and the safety/efficacy of interventions on an individual level. Serial sampling revealed that unexpectedly high values in heathy individuals can be observed, which urges caution when interpreting AD plasma biomarkers based on a single test result. |
| Author | Díaz–Garzón, Jorge Jonker, Niels Brum, Wagner S. Zimmer, Eduardo R. Calle, Pilar Fernández Zetterberg, Henrik Carobene, Anna Montoliu‐Gaya, Laia Lantero‐Rodriguez, Juan Bartlett, William A. Coşkun, Abdurrahman Blennow, Kaj di Molfetta, Guiglielmo Karikari, Thomas K. Jeromin, Andreas Benedet, Andrea L. Ashton, Nicholas J. Sandberg, Sverre Aarsand, Aasne K. Simrén, Joel |
| AuthorAffiliation | 11 ALZpath. Inc Carlsbad California USA 10 McGill Centre for Studies in Aging McGill University Verdun Quebec Canada 16 School of Medicine, Department of Medical Biochemistry Acibadem Mehmet Ali Aydınlar University Istanbul Turkey 18 Department of Neurodegenerative Disease UCL Institute of Neurology London UK 2 Department of Biochemistry Universidade Federal do Rio Grande do Sul (UFRGS) Porto Alegre Brazil 1 Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology The Sahlgrenska Academy at the University of Gothenburg Mölndal Sweden 15 Department of Laboratory Medicine La Paz University Hospital Madrid Spain 8 Department of Pharmacology Universidade Federal do Rio Grande do Sul (UFRGS) Porto Alegre Brazil 9 Graduate Program in Biological Sciences Universidade Federal do Rio Grande do Sul (UFRGS) Porto Alegre Brazil 3 King's College London, Institute of Psychiatry Psychology and Neuroscience Maurice Wohl Institute Clinical Neuroscience Institute London UK 17 Certe Wi |
| AuthorAffiliation_xml | – name: 1 Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology The Sahlgrenska Academy at the University of Gothenburg Mölndal Sweden – name: 18 Department of Neurodegenerative Disease UCL Institute of Neurology London UK – name: 8 Department of Pharmacology Universidade Federal do Rio Grande do Sul (UFRGS) Porto Alegre Brazil – name: 13 The Norwegian Organization for Quality Improvement of Laboratory Examinations (NOKLUS) Haraldsplass Deaconess Hospital Bergen Norway – name: 2 Department of Biochemistry Universidade Federal do Rio Grande do Sul (UFRGS) Porto Alegre Brazil – name: 3 King's College London, Institute of Psychiatry Psychology and Neuroscience Maurice Wohl Institute Clinical Neuroscience Institute London UK – name: 19 UK Dementia Research Institute at UCL London UK – name: 7 Department of Psychiatry University of Pittsburgh Pittsburgh Pennsylvania USA – name: 15 Department of Laboratory Medicine La Paz University Hospital Madrid Spain – name: 9 Graduate Program in Biological Sciences Universidade Federal do Rio Grande do Sul (UFRGS) Porto Alegre Brazil – name: 22 Department of Global Health and Primary Care, Faculty of Medicine University of Bergen Bergen Norway – name: 4 NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation London UK – name: 21 Wisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health University of Wisconsin–Madison Madison Wisconsin USA – name: 11 ALZpath. Inc Carlsbad California USA – name: 16 School of Medicine, Department of Medical Biochemistry Acibadem Mehmet Ali Aydınlar University Istanbul Turkey – name: 10 McGill Centre for Studies in Aging McGill University Verdun Quebec Canada – name: 20 Hong Kong Center for Neurodegenerative Diseases Hong Kong China – name: 6 Clinical Neurochemistry Laboratory Sahlgrenska University Hospital Mölndal Sweden – name: 14 School of Science and Engineering University of Dundee Dundee UK – name: 12 European Federation of Clinical Chemistry and Laboratory Medicine Working Group on Biological Variation Milan Italy – name: 23 Laboratory Medicine IRCCS San Raffaele Scientific Institute Milan Italy – name: 5 Centre for Age‐Related Medicine Stavanger University Hospital Stavanger Norway – name: 17 Certe Wilhelmina Ziekenhuis Assen Assen the Netherlands |
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| Copyright_xml | – notice: 2023 The Authors. published by Wiley Periodicals LLC on behalf of Alzheimer's Association. – notice: 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association. – notice: 2024. This work is published 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. |
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| Keywords | amyloid biological variation reference change values plasma biomarkers analytical variation neurofilament light glial fibrillary acidic protein phosphorylated tau |
| Language | English |
| License | Attribution 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
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| Snippet | INTRODUCTION
Blood biomarkers have proven useful in Alzheimer's disease (AD) research. However, little is known about their biological variation (BV), which... Blood biomarkers have proven useful in Alzheimer's disease (AD) research. However, little is known about their biological variation (BV), which improves the... INTRODUCTION Blood biomarkers have proven useful in Alzheimer's disease (AD) research. However, little is known about their biological variation (BV), which... INTRODUCTION: Blood biomarkers have proven useful in Alzheimer's disease (AD) research. However, little is known about their biological variation (BV), which... |
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| SubjectTerms | Alzheimer Disease - diagnosis Alzheimer's disease amyloid Amyloid beta-Peptides analytical variation Biological markers biological variation Biomarkers Changes Clinical research Disease Progression Efficacy Glial Fibrillary Acidic Protein Humans Intervention Laboratories neurofilament light Neurosciences Neurovetenskaper Pathology phosphorylated tau plasma biomarkers reference change values tau Proteins Values Variability Variants |
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| Title | Biological variation estimates of Alzheimer's disease plasma biomarkers in healthy individuals |
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