Plasma biomarkers show potential in detecting and monitoring Alzheimer's pathology in preclinical stages, aiding early interventions.
A fully automated plasma biomarker panel detected amyloid-beta positivity and monitored early amyloid accumulation in middle-aged cognitively unimpaired adults at risk forThis study involved 400 middle-aged CU individuals at risk for the disease from the Alzheimer's and Families study longitudinal cohort, of whom 135 were Aβ-positive and 265 were Aβ-negative ; 54 of 342 participants with PET imaging were PET A+, and assessments were performed every 3 years.
Plasma biomarkers — Aβ42/40, p-tau181, glial fibrillary acidic protein, neurofilament light, p-tau217, ApoE4, and p-tau181/Aβ42 and p-tau217/Aβ42 ratios — were quantified via fully automated immunoassays; cerebrospinal fluid biomarkers included Aβ42/40, p-tau181, and total tau; MRI assessed cortical thickness, and amyloid PET quantified Aβ deposition. Aβ status was defined using CSF Aβ42/40 ratio . Cognitive function was assessed using the modified Preclinical Alzheimer's Cognitive Composite. The primary outcome was the performance of plasma biomarkers in detecting Aβ pathology; secondary outcomes included longitudinal associations between biomarkers and changes in Aβ, tau, neurodegeneration, and cognitive pathology.Plasma p-tau217/Aβ42 showed the highest accuracy in detecting PET Aβ positivity , significantly outperforming all other biomarkers. All plasma biomarkers were significantly different between A+ and A− individuals, with plasma p-tau217/Aβ42 and p-tau217 showing the largest effect sizes (ηPlasma Aβ42/40 was highly sensitive to random variability, affecting its reliability in detecting Aβ pathology, particularly when the coefficient of variation exceeded 9% for PET or 16% for CSF classification."Fully automated immunoassay-based blood biomarkers offer significant diagnostic, prognostic, and monitoring capabilities for CU individuals at risk of AD even in a relatively short time span," the authors of the study wrote.This study was limited by unmeasured factors such as lifestyle factors, occupational exposures, or genetic variants, which may still influence plasma biomarker levels and Aβ accumulation. Results from a middle-aged, at-risk cohort with low progression tolimited the generalisability to older populations. As a single-centre study, the results need to be replicated in larger, independent cohorts.This study was funded by the European Research Council, ERA PerMed-ERA NET, and the Generalitat de Catalunya. Some authors reported receiving consultancy/speaker fees from several pharmaceutical organisations. This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.González-Escalante A, Milà-Alomà M, Brum WS, et al. A plasma biomarker panel for detecting early amyloid-β accumulation and its changes in middle-aged cognitively unimpaired individuals at risk for Alzheimer's disease. eBioMedicine. Published online May 24, 2025. doi:10.1016/j.ebiom.2025.105741All material on this website is protected by copyright, Copyright © 1994-2025 by WebMD LLC. This website also contains material copyrighted by 3rd parties.
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