Journal
ALZHEIMERS & DEMENTIA
Volume 18, Issue 2, Pages 283-293Publisher
WILEY
DOI: 10.1002/alz.12395
Keywords
Alzheimer's disease; amyloid; A beta 42/A beta 40; blood biomarkers; neurofilament light; p-tau217
Categories
Funding
- Swedish Research Council [2016-00906]
- Knut and AliceWallenberg Foundation [2017-0383]
- Marianne and MarcusWallenberg Foundation [2015.0125]
- Swedish Alzheimer Foundation [AF-745911, AF-846521]
- SwedishBrain Foundation [FO2019-0326]
- Parkinson Foundation of Sweden [1280/20]
- Skane University Hospital Foundation [2020-O000028]
- Regionalt Forskningsstod [2020-0314]
- Konung GustafV:s och Drottning Victorias Frimurarestiftelse
- Swedish federal government [2018-Projekt0279]
- European Commission (Marie Curie International Training Network, JPND)
- Health Holland
- Dutch Research Council (ZonMW)
- AlzheimerDrugDiscovery Foundation
- Selfridges Group Foundation
- AlzheimerNetherlands
- AlzheimerAssociation
- Strategic Research Area MultiPark (MultidisciplinaryResearch inParkinson's disease) at Lund University
- Bundy Academy
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The combination of blood Aβ 42 / Aβ 40 and p-tau217 showed relatively high accuracy in discriminating Aβ status, with p-tau217 demonstrating the strongest associations with Aβ pathology in MCI but not in CU.
Introduction: We studied usefulness of combining blood amyloid beta A(beta)42/A beta 40, phosphorylated tau (p-tau)217, and neurofilament light (NfL) to detect abnormal brain A beta deposition in different stages of early Alzheimer's disease (AD). Methods: Plasma biomarkers were measured using mass spectrometry (A beta 42/A beta 40) 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 A beta 42/A beta 40 and p-tau217 detected abnormal brain A beta status with area under the curve (AUC) of 0.83 to 0.86. In MCI, the models including p-tau217 alone or A beta 42/A beta 40 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.shinyappas.io/PredictAAbplasma/). Discussion:A combination of plasma A beta 42/A beta 40 and p-tau217 discriminated A beta status with relatively high accuracy, whereas p-tau217 showed strongest associations with A beta pathology in MCI but not in CU.
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