Detecting amyloid positivity in early Alzheimer's disease using combinations of plasma Aβ42/Aβ40 and p‐tau
Open accessAbstract
Introduction: We studied usefulness of combining blood amyloid beta (Aβ)42/Aβ40, phosphorylated tau (p‐tau)217, and neurofilament light (NfL) to detect abnormal brain Aβ deposition in different stages of early Alzheimer's disease (AD). Methods: Plasma biomarkers were measured using mass spectrometry (Aβ42/Aβ40) and immunoassays (p‐tau217 and NfL) in cognitively unimpaired individuals (CU, N = 591) and patients with mild cognitive impairment (MCI, N = 304) from two independent cohorts (BioFINDER‐1, BioFINDER‐2). Results: In CU, a combination of plasma Aβ42/Aβ40 and p‐tau217 detected abnormal brain Aβ status with area under the curve (AUC) of 0.83 to 0.86. In MCI, the models including p‐tau217 alone or Aβ42/Aβ40 and p‐tau217 had similar AUCs (0.86–0.88); however, the latter showed improved model fit. The models were implemented in an online application providing individualized risk assessments ( https://brainapps.shinyapps.io/PredictABplasma/ ). Discussion: A combination of plasma Aβ42/Aβ40 and p‐tau217 discriminated Aβ status with relatively high accuracy, whereas p‐tau217 showed strongest associations with Aβ pathology in MCI but not in CU.
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Previous research attempted to develop algorithms combining multiple factors and showed better and more robust performance in predicting Aβ positivity of Alzheimer's disease.
“Previous research attempted to develop algorithms combining multiple factors and showed better and more robust performance in predicting Aβ positivity of Alzheimer’s disease.”
From Integrated algorithm combining plasma biomarkers and cognitive assessments accurately predicts brain β-amyloid pathology (2023) · cites this paper as [14]
Detection of Aβ positivity using mass spectrometry %p-tau217 in cognitively normal cohorts appears better than what has been reported when using plasma p-tau217 immunoassays.
“Detection of Aβ positivity using mass spectrometry %p-tau217 in cognitively normal cohorts appears better than what has been reported when using plasma p-tau217 immunoassays, although this must be confirmed in head-to-head studies22,23,48–50.”
From Highly accurate blood test for Alzheimer's disease is similar or superior to clinical cerebrospinal fluid tests (2024) · cites this paper as [50]
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- Authors
- Janelidze, S., Palmqvist, S., Leuzy, A., Stomrud, E., Verberk, I. M. W., Zetterberg, H., Ashton, N. J., Pesini, P., Sarasa, L., Allué, J. A., Teunissen, C. E., Dage, J. L., Blennow, K., Mattsson‐Carlgren, N., & Hansson, O.
- Affiliations
- Lund University (SE)
- Amsterdam Neuroscience (NL)
- Sahlgrenska University Hospital (SE)
- King's College London (GB)
- Araclon Biotech Ltd. Zaragoza Spain
- Eli Lilly (United States) (US)
- Clinical Memory Research Unit, Department of Clinical Sciences Malmö Lund University Lund Sweden
- Corresponding author
- Hansson, Oskar
- ORCID
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2021-06-20
- Volume
- 18
- Issue
- 2
- Pages
- 283-293
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- OpenAlex
- W3174265554
- Cited by
- 188
- References
- 14
- Citations by year
- 2026: 16 · 2025: 49 · 2024: 53 · 2023: 40 · 2022: 27 · 2021: 3
- FWCI
- 22.40
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Alzheimer s & Dementia (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion, other-oa)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion, other-oa)
- UCL Discovery (University College London) (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- IUScholarWorks (Indiana University) (submittedVersion, cc-by-nc)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- Vetenskapsrådet (2016‐00906)
- Knut och Alice Wallenbergs Stiftelse (2017‐0383)
- Marianne and Marcus Wallenberg Foundation (2015.0125)
- Hjärnfonden (FO2019‐0326)
- Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse
- Alzheimer Nederland
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- early Alzheimer's disease, amyloid-beta
- MeSH terms
- Alzheimer Disease, Amyloid, Amyloidosis, Humans, Peptide Fragments, Biomarkers, Amyloid beta-Peptides, tau Proteins, Positron-Emission Tomography, Cognitive Dysfunction
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