Detecting amyloid positivity in early Alzheimer's disease using combinations of plasma A beta 42/A beta 40 and p-tau
Janelidze, Shorena; Palmqvist, Sebastian; Leuzy, Antoine; Stomrud, Erik; Verberk, Inge M. W.; Zetterberg, Henrik; Ashton, Nicholas J.; Pesini, Pedro; Sarasa, Leticia; Allue, Jose Antonio; Teunissen, Charlotte E.; Dage, Jeffrey L.; Blennow, KAJ; Mattsson-Ca
ALZHEIMERS & DEMENTIA
2021
VL / 18 - BP / - EP /
abstract
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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