Clinical and analytical comparison of six Simoa assays for plasma P-tau isoforms P-tau181, P-tau217, and P-tau231

Alzheimer s Research & Therapy, Journal Year: 2021, Volume and Issue: 13(1)

Published: Dec. 1, 2021

Studies using different assays and technologies showed highly promising diagnostic value of plasma phosphorylated (P-)tau levels for Alzheimer's disease (AD). We aimed to compare six P-tau Simoa assays, including three P-tau181 (Eli Lilly, ADx, Quanterix), one P-tau217 Lilly), two P-tau231 (ADx, Gothenburg).We studied the analytical (sensitivity, precision, parallelism, dilution linearity, recovery) clinical (40 AD dementia patients, age 66±8years, 50%F; 40 age- sex-matched controls) performance assays.All robust performance, particularly Eli Lilly; Gothenburg all differentiate from controls, with AUCs 0.936-0.995 (P-tau231 ADx: AUC = 0.719). Results obtained Lilly assay, assay strongly correlated (Spearman's rho > 0.86), while correlations ADx results were moderate (rho < 0.65).P-tau isoforms can be measured robustly by several novel high-sensitive assays.

Language: Английский

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Plasma Aβ42/40 ratio, p‐tau181, GFAP, and NfL across the Alzheimer's disease continuum: A cross‐sectional and longitudinal study in the AIBL cohort

Alzheimer s & Dementia, Journal Year: 2022, Volume and Issue: 19(4), P. 1117 - 1134

Published: July 21, 2022

Plasma amyloid beta (Aβ)1-42/Aβ1-40 ratio, phosphorylated-tau181 (p-tau181), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) are putative blood biomarkers for Alzheimer's disease (AD). However, head-to-head cross-sectional longitudinal comparisons of the aforementioned across AD continuum lacking.Plasma Aβ1-42, Aβ1-40, p-tau181, GFAP, NfL were measured utilizing Single Molecule Array (Simoa) platform compared cross-sectionally continuum, wherein Aβ-PET (positron emission tomography)-negative cognitively unimpaired (CU Aβ-, n = 81) mild cognitive impairment (MCI 26) participants with Aβ-PET-positive Aβ+, 39; MCI 33; 46) from Australian Imaging, Biomarker & Lifestyle Flagship Study Ageing (AIBL) cohort. Longitudinal plasma biomarker changes also assessed in (n 27) 29) CU 120) participants. In addition, associations between baseline levels prospective decline load over a 7 to 10-year duration.Lower Aβ1-42/Aβ1-40 ratio elevated p-tau181 GFAP observed whereas was Aβ+ Aβ- Aβ-. Among biomarkers, models without risk factors (age, sex, apolipoprotein E (APOE) ε4 carrier status), performed equivalent or better than other predicting brain Aβ-/+ status continuum. factors, panel Aβ1-42/Aβ1-40, any alone Longitudinally, altered CU, CU. lower higher associated increased prospectively.These findings suggest that longitudinally, along prospectively load. although an may have superior predictive capability continuum.Area under curve (AUC) ≥ AUC Aβ42/40, PET (Aβ-/+). Aβ42/40+p-tau181+GFAP Aβ42/40/p-tau181/GFAP/NfL Aβ-/+. versus decline. Aβ prospectively.

Language: Английский

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

Alzheimer s & Dementia, Journal Year: 2021, Volume and Issue: 18(2), P. 283 - 293

Published: June 20, 2021

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 early Alzheimer's disease (AD).Plasma biomarkers were measured using mass spectrometry (Aβ42/Aβ40) immunoassays (p-tau217 NfL) cognitively unimpaired individuals (CU, N = 591) patients with mild cognitive impairment (MCI, 304) from two independent cohorts (BioFINDER-1, BioFINDER-2).In CU, a combination plasma Aβ42/Aβ40 p-tau217 detected status area under the curve (AUC) 0.83 0.86. In MCI, models including alone or had similar AUCs (0.86-0.88); however, latter showed improved model fit. The implemented an online application providing individualized risk assessments (https://brainapps.shinyapps.io/PredictABplasma/).A discriminated relatively high accuracy, whereas strongest associations pathology MCI but not CU.

Language: Английский

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Differential levels of plasma biomarkers of neurodegeneration in Lewy body dementia, Alzheimer’s disease, frontotemporal dementia and progressive supranuclear palsy

Journal of Neurology Neurosurgery & Psychiatry, Journal Year: 2022, Volume and Issue: 93(6), P. 651 - 658

Published: Jan. 25, 2022

This longitudinal study compared emerging plasma biomarkers for neurodegenerative disease between controls, patients with Alzheimer's (AD), Lewy body dementia (LBD), frontotemporal (FTD) and progressive supranuclear palsy (PSP).

Language: Английский

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Blood-based biomarkers for Alzheimer’s disease: Current state and future use in a transformed global healthcare landscape

Neuron, Journal Year: 2023, Volume and Issue: 111(18), P. 2781 - 2799

Published: June 8, 2023

Language: Английский

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