Detecting amyloid positivity in early Alzheimer's disease using combinations of plasma Aβ42/Aβ40 and p‐tau

Abstract

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 implementedThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Phospho‐specific plasma p‐tau181 assay detects clinical as well as asymptomatic Alzheimer's disease

“… 13 , 43 In addition to plasma p‐tau181, plasma p‐tau217 and p‐tau231 have also shown promise as blood‐based markers of asymptomatic AD. 5 , 6 , 9 , 10 , 11 , 44 , 45 In line with observations of the recent pilot study, 15 the ADx prototype p‐tau231 assay could not distinguish AD patients from controls as accurately as the p‐tau181 assay. We now also demonstrated that it performs worse than p‐tau181 in the asymptomatic phase of AD.…”

“…Contrarily, two other studies reported only weak correlations which were restricted to small regions within the precuneus, temporal and superior‐frontal areas 13,43 . In addition to plasma p‐tau181, plasma p‐tau217 and p‐tau231 have also shown promise as blood‐based markers of asymptomatic AD 5,6,9–11,44,45 . In line with observations of the recent pilot study, 15 the ADx prototype p‐tau231 assay could not distinguish AD patients from controls as accurately as the p‐tau181 assay.…”

Blood-Based Biomarkers for Alzheimer’s Disease Diagnosis and Progression: An Overview

“…In this respect, Janelidze et al conducted an investigation on 176 MCI, 89 subjective cognitive decline (SCD), and 225 healthy individuals from the BioFINDER-2 cohort, and reported that increased levels of plasma of p-tau217 could discriminate preclinical stages of AD prior to any deposition of PET-detectable neurofibrils [ 52 ]. Moreover, further evidence from BioFINDER-1 and BioFINDER-2 studies showed that a combination of p-tau217 and plasma Aβ 1–42 /Aβ 1–40 ratio was able to detect Aβ pathology both in MCI and healthy individuals [ 53 ].…”

Head-to-Head Comparison of 8 Plasma Amyloid-β 42/40 Assays in Alzheimer Disease

“…All BioFINDER study participants underwent measurements of plasma concentrations of Aβ42 and Aβ40 using the IP-MSbased method developed at Washington University, St Louis, Missouri (IP-MS-WashU), the antibody-free liquid chromatography-MS developed by Araclon Biotech, Zaragoza, Spain (LC-MS-Arc), Elecsys immunoassays from Roche Diagnostics, Penzberg, Germany (IA-Elc), immunoassays from Euroimmun, Lübeck, Germany (IA-EI), and N4PE Simoa immunoassays (IA-N4PE) developed by Amsterdam University Medical Center, Amsterdam, the Netherlands, and ADx Neurosciences, Ghent, Belgium, and commercially available from Quanterix, Billerica, Massachusetts, in the specific laboratories. [4][5][6][7][8][10][11][12] In subcohorts of study participants, plasma samples were analyzed using the IP-MS-based method developed by Shimadzu, Kyoto, Japan (IP-MS-Shim; n = 200; subcohort 1), as well as the IP-MS-based methods developed at the University of Gothenburg, Gothenburg, Sweden (IP-MS-UGOT), and another Simoa immunoassay from Quanterix (IA-Quan; n = 227; subcohort 2). 3,4,11 Aβ42 and Aβ40 levels in CSF were determined with Elecsys CSF immunoassays.…”