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Concordance between different amyloid immunoassays and visual amyloid positron emission tomographic assessment.
Open accessAbstract
Importance: Visual assessment of amyloid positron emission tomographic (PET) images has been approved by regulatory authorities for clinical use. Several immunoassays have been developed to measure β-amyloid (Aβ) 42 in cerebrospinal fluid (CSF). The agreement between CSF Aβ42 measures from different immunoassays and visual PET readings may influence the use of CSF biomarkers and/or amyloid PET assessment in clinical practice and trials. Objective: To determine the concordance between CSF Aβ42 levels measured using 5 different immunoassays and visual amyloid PET analysis. Design, Setting, and Participants: The study included 262 patients with mild cognitive impairment or subjective cognitive decline from the Swedish BioFINDER (Biomarkers for Identifying Neurodegenerative Disorders Early and Reliably) cohort (recruited from September 1, 2010, through December 31, 2014) who had undergone flutemetamol F 18 ([18F]flutemetamol)-labeled PET. Levels of CSF Aβ42 were analyzed using the classic INNOTEST and the newer modified INNOTEST, fully automated Lumipulse (FL), EUROIMMUN (EI), and Meso Scale Discovery (MSD) assays. Concentrations of CSF Aβ were assessed using an antibody-independent mass spectrometry-based reference measurement procedure. Main Outcomes and Measures: The concordance of CSF Aβ42 levels and Aβ42:Aβ40 and Aβ42:tau ratios with visual [18F]flutemetamol PET status. Results: Of 262 participants (mean [SD] age, 70.9 [5.5] years), 108 were women (41.2%) and 154 were men (58.8%). The mass spectrometry-derived Aβ42 values showed higher correlations with the modified Aβ42-INNOTEST (r = 0.97), Aβ42-FL (r = 0.93), Aβ42-EI (r = 0.93), and Aβ42-MSD (r = 0.95) assays compared with the classic Aβ42-INNOTEST assay (r = 0.88; P ≤ .01). The signal in the classic Aβ42-INNOTEST assay was partly quenched by recombinant Aβ1-40 peptide. However, the classic Aβ42-INNOTEST assay showed better concordance with visual [18F]flutemetamol PET status (area under the receiver operating characteristic curve [AUC], 0.92) compared with the newer assays (AUCs, 0.87-0.89; P ≤ .01). The accuracies of the newer assays improved significantly when Aβ42:Aβ40 (AUCs, 0.93-0.95; P ≤ .01), Aβ42 to total tau (T-tau) (AUCs, 0.94; P ≤ .05), or Aβ42 to phosphorylated tau (P-tau) (AUCs, 0.94-0.95; P ≤ .001) ratios were used. A combination of the Aβ42:Aβ40 ratio and T-tau or P-tau level did not improve the accuracy compared with the ratio alone. Conclusions and Relevance: Concentrations of CSF Aβ42 derived from the new immunoassays (modified INNOTEST, FL, EI, and MSD) may correlate better with the antibody-independent mass spectrometry-based reference measurement procedure and may show improved agreement with visual [18F]flutemetamol PET assessment when using the Aβ42:Aβ40 or Aβ42:tau ratios. These findings suggest the benefit of implementing the CSF Aβ42:Aβ40 or Aβ42:tau ratios as a biomarker of amyloid deposition in clinical practice and trials.
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“Recently, fully automated immunoassays have been developed by several different vendors with improved reliability and precision for CSF Aβ and tau species.23,24,25”
From Performance of Fully Automated Plasma Assays as Screening Tests for Alzheimer Disease–Related β-Amyloid Status (2019) · cites this paper as [25]
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Metadata
- Authors
- Janelidze, S., Pannee, J., Mikulskis, A., Chiao, P., Zetterberg, H., Blennow, K., & Hansson, O.
- Affiliations
- Lund University (SE)
- University of Gothenburg (SE)
- Biogen (United States) (US)
- Sahlgrenska University Hospital (SE)
- Corresponding author
- Janelidze, Shorena
- Venue
- JAMA Neurology
- Publisher
- American Medical Association (AMA)
- Published
- 2017-12-01
- Volume
- 74
- Issue
- 12
- Pages
- 1492
- ISSN
- 2168-6149 (ISSN-L)
- PMC
- PMC5822196
- OpenAlex
- W2767595531
- Cited by
- 147
- References
- 36
- Citations by year
- 2026: 9 · 2025: 13 · 2024: 19 · 2023: 13 · 2022: 19 · 2021: 24 · 2020: 23 · 2019: 15 · 2018: 12
- FWCI
- 11.24
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA Neurology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- Australian Government
- Vetenskapsrådet
- Fujirebio Europe
- Marcus och Amalia Wallenbergs minnesfond
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Health Professions › Medical Laboratory Technology › Clinical Laboratory Practices and Quality Control
- Keywords
- amyloid PET, amyloid-beta 42, cerebrospinal fluid biomarkers, 18F-flutemetamol, Meso Scale Discovery, Aβ42/Aβ40 ratio, mild cognitive impairment
- MeSH terms
- Aged, Amyloid, Aniline Compounds, Cerebral Cortex, Female, Humans, Immunoassay, Male, Peptide Fragments, ROC Curve, Sweden, Cohort Studies, Amyloid beta-Peptides, tau Proteins, Radiopharmaceuticals, Area Under Curve, Positron-Emission Tomography, Benzothiazoles, Cognitive Dysfunction
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