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Plasma phosphorylated-tau217 (p-tau217) has been shown to be one of the most accurate diagnostic markers for Alzheimer's disease. No studies have compared the clinical performance of p-tau217 as assessed by the fully automated Lumipulse and single molecule array (SIMOA) AlZpath p-tau217. The study included 392 participants, 162 with Alzheimer's disease, 70 with other neurodegenerative diseases with CSF biomarkers and 160 healthy controls. Plasma p-tau217 levels were measured using the Lumipulse and ALZpath SIMOA assays. The ability of p-tau217 assessed by both techniques to discriminate Alzheimer's disease from other neurodegenerative diseases and controls was investigated using receiver operating characteristic analyses. The p-tau217 levels measured by the two techniques demonstrated a strong correlation, showing a consistent relationship with CSF p-tau181 levels. In head-to-head comparison, Lumipulse and SIMOA showed similar diagnostic accuracy for differentiating Alzheimer's disease from other neurodegenerative diseases [area under the curve (AUC) 0.952, 95% confidence interval (CI) 0.927-0.978 versus 0.955, 95% CI 0.928-0.982, respectively] and healthy controls (AUC 0.938, 95% CI 0.910-0.966 and 0.937, 95% CI 0.907-0.967 for both assays). This study demonstrated the high precision and diagnostic accuracy of p-tau217 for the clinical diagnosis of Alzheimer's disease using fully automated or semi-automated techniques., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Introduction: Blood-based biomarkers for Alzheimer's disease (AD) have been widely studied, but direct comparisons of several biomarkers in clinical settings remain limited., Methods: In this cross-sectional study, plasma biomarkers from 197 participants in the BIODEGMAR cohort (Hospital del Mar, Barcelona) were analyzed. Participants were classified based on AD cerebrospinal fluid (CSF) core biomarkers. We assessed the ability of plasma p-tau181, p-tau217, p-tau231, t-tau, and Aβ42/40 to classify Aβ pathology status., Results: Plasma p-tau biomarkers had a greater diagnostic performance and larger effect sizes compared to t-tau and Aβ42/40 assays in detecting Aβ pathology. Among them, plasma p-tau217 consistently outperformed the others, demonstrating superior area under the curves. Furthermore, p-tau217 showed the strongest correlation between plasma and CSF levels, underscoring its potential as a reliable surrogate for CSF biomarkers., Discussion: Several plasma biomarkers, targeting different epitopes and using different platforms, demonstrated high performance in detecting AD in a memory clinic setting., Highlights: Plasma p-tau biomarkers demonstrated higher diagnostic performance and larger effect sizes than t-tau and Aβ42/40 assays in detecting Alzheimer's disease. Among the p-tau biomarkers, p-tau217 assays consistently outperformed the others, providing superior classification of Aβ pathology status across different phosphorylation sites. p-tau217 assays showed the strongest correlation between plasma and CSF levels, indicating its potential as a reliable surrogate for CSF biomarkers. Several plasma p-tau biomarkers can be used in a specialized memory clinic to accurately detect Alzheimer's disease., (© 2025 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

In Alzheimer's disease (AD), Aβ triggers p-tau secretion, which drives tau aggregation. Therefore, it is critical to characterize modulators of Aβ-related p-tau increases which may alter AD trajectories. Here, we assessed whether factors known to alter tau levels in AD modulate the association between fibrillar Aβ and secreted p-tau 181 determined in the cerebrospinal fluid (CSF). To assess potentially modulating effects of female sex, younger age, and ApoE4, we included 322 ADNI participants with cross-sectional/longitudinal p-tau 181 . To determine effects of microglial activation on p-tau 181 , we included 454 subjects with cross-sectional CSF sTREM2. Running ANCOVAs for nominal and linear regressions for metric variables, we found that women had higher Aβ-related p-tau 181 levels. Higher sTREM2 was associated with elevated p-tau 181 , with stronger associations in women. Similarly, ApoE4 was related to higher p-tau 181 levels and faster p-tau 181 increases, with stronger effects in female ApoE4 carriers. Our results show that sex alone modulates the Aβ to p-tau axis, where women show higher Aβ-dependent p-tau secretion, potentially driven by elevated sTREM2-related microglial activation and stronger effects of ApoE4 carriership in women., Competing Interests: Disclosure and competing interests statement. The authors declare no competing interests., (© 2025. The Author(s).)