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Amyloid β concentrations and stable isotope labeling kinetics of human plasma specific to central nervous system amyloidosis
Open accessAbstract
Introduction: Cerebrospinal fluid analysis and other measurements of amyloidosis, such as amyloid‐binding positron emission tomography studies, are limited by cost and availability. There is a need for a more practical amyloid β (Aβ) biomarker for central nervous system amyloid deposition. Methods: We adapted our previously reported stable isotope labeling kinetics protocol to analyze the turnover kinetics and concentrations of Aβ38, Aβ40, and Aβ42 in human plasma. Results: Aβ isoforms have a half‐life of approximately 3 hours in plasma. Aβ38 demonstrated faster turnover kinetics compared with Aβ40 and Aβ42. Faster fractional turnover of Aβ42 relative to Aβ40 and lower Aβ42 and Aβ42/Aβ40 concentrations in amyloid‐positive participants were observed. Discussion: Blood plasma Aβ42 shows similar amyloid‐associated alterations as we have previously reported in cerebrospinal fluid, suggesting a blood‐brain transportation mechanism of Aβ. The stability and sensitivity of plasma Aβ measurements suggest this may be a useful screening test for central nervous system amyloidosis.
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“an 8-year follow-up study of 599 volunteers (average age 70 years) in Australia found that cognitively normal PET amyloid-positive people had an elevated risk of developing Alzheimer's disease compared with amyloid negative (17·7% vs 8·1%; OR 2·4, 95% CI 1·5–4·0).184”
From Dementia prevention, intervention, and care: 2020 report of the Lancet Commission (2020) · cites this paper as [184]
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“Plasma Aβ measures now show promise [202,203].”
From NIA‐AA Research Framework: Toward a biological definition of Alzheimer's disease (2018) · cites this paper as [202]
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“While imaging/CSF biomarker data on subsets of individuals from well-designed community-based cohorts would provide additional research value, incorporating biomarkers on a large scale in many settings will require low-cost and minimally invasive biomarkers (e.g., blood or saliva) that are now emerging [202–205].”
From NIA‐AA Research Framework: Toward a biological definition of Alzheimer's disease (2018) · cites this paper as [202]
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“Over 80% of the 266 people who were PET amyloid-positive did not go onto develop a cognitive impairment within 8 years, showing positive status does not predict impairment for most people in a timeframe that might be a useful prognostic window.”
From Dementia prevention, intervention, and care: 2020 report of the Lancet Commission (2020) · cites this paper as [184]
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“Follow-up at 5 years of amyloid-positive participants with normal cognition or mild cognitive impairment versus amyloid negative people found the same pattern of increased risk (2·6, 1·4–4·9).”
From Dementia prevention, intervention, and care: 2020 report of the Lancet Commission (2020) · cites this paper as [184]
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“Risk also increases per 1 year of age (HR 1·05, 95% CI 0·55–2·0/year), and APOEε4 status (2·6, 1·4–5·0).184”
From Dementia prevention, intervention, and care: 2020 report of the Lancet Commission (2020) · cites this paper as [184]
Experimental — accuracy not yet measuredIn the citing paper
“Blood biomarkers for the presymptomatic phase of Alzheimer’s disease are largely lacking, although recent progress in the analysis of amyloid-β, tau, and neurofilament light chain (NfL) in the blood have been reported5–10.”
From Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer’s disease (2019) · cites this paper as [8]
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“Recent studies demonstrate the ability to detect CNS Aβ deposition via the use of plasma assessment of Aβ species”
From Alzheimer Disease: An Update on Pathobiology and Treatment Strategies (2019) · cites this paper as Ovod et al., 2017
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“Most recently, 2 independent groups demonstrated improved accuracy for plasma Aβ42/Aβ40 using immunoprecipitation–mass spectrometry assays.19,20”
From Performance of Fully Automated Plasma Assays as Screening Tests for Alzheimer Disease–Related β-Amyloid Status (2019) · cites this paper as [20]
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“In mass spectrometry–based techniques, 2 recent studies have provided overall better accuracies for plasma Aβ42/Aβ40 (AUC, 0.84-0.97 depending on population and reference standard).19,20”
From Performance of Fully Automated Plasma Assays as Screening Tests for Alzheimer Disease–Related β-Amyloid Status (2019) · cites this paper as [20]
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Metadata
- Authors
- Ovod, V., Ramsey, K. N., Mawuenyega, K. G., Bollinger, J. G., Hicks, T., Schneider, T., Sullivan, M., Paumier, K., Holtzman, D. M., Morris, J. C., Benzinger, T., Fagan, A. M., Patterson, B. W., & Bateman, R. J.
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- Bateman, Randall J.
- ORCID
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2017-07-19
- Volume
- 13
- Issue
- 8
- Pages
- 841-849
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- PMC
- PMC5567785
- OpenAlex
- W2736518852
- Cited by
- 585
- References
- 18
- Citations by year
- 2026: 44 · 2025: 44 · 2024: 74 · 2023: 65 · 2022: 84 · 2021: 85 · 2020: 70 · 2019: 66 · 2018: 47 · 2017: 2
- FWCI
- 37.40
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Alzheimer s & Dementia (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- MetLife Foundation
- AbbVie
- Amgen
- AstraZeneca
- Biogen
- Eisai
- Pfizer
- Sanofi
- Avid Radiopharmaceuticals
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Internal Medicine › Amyloidosis: Diagnosis, Treatment, Outcomes
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- amyloid-beta, plasma amyloid-beta
- MeSH terms
- Aged, Amyloidosis, Chromatography, Liquid, Humans, Isotope Labeling, Kinetics, Peptide Fragments, Prospective Studies, ROC Curve, Mass Spectrometry, Biomarkers, Single-Blind Method, Amyloid beta-Peptides, Area Under Curve, Immunoprecipitation
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