| Title: |
Diagnostic performance of plasma pTau217/Aβ42 ratio and a three-zone threshold model for Alzheimer's disease |
| Authors: |
Benussi, Alberto; Michelutti, Marco; Lombardo, Tiziana Maria Isabella; Toffoletto, Barbara; Palacino, Federica; Cenacchi, Valentina; Pelusi, Luca; Capacchione, Francesco; Menichelli, Alina; Perego, Alberto; Sirianni, Francesca; Cattaruzza, Tatiana; Manganotti, Paolo |
| Contributors: |
Benussi, Alberto; Michelutti, Marco; Lombardo, Tiziana Maria Isabella; Toffoletto, Barbara; Palacino, Federica; Cenacchi, Valentina; Pelusi, Luca; Capacchione, Francesco; Menichelli, Alina; Perego, Alberto; Sirianni, Francesca; Cattaruzza, Tatiana; Manganotti, Paolo |
| Publication Year: |
2026 |
| Collection: |
Università degli studi di Trieste: ArTS (Archivio della ricerca di Trieste) |
| Subject Terms: |
Alzheimer’s disease; Amyloid pathology; Blood-based biomarker; Diagnostic accuracy; Mild cognitive impairment; Non-invasive diagnostic; PTau(217)/Aβ(42) ratio; Plasma pTau(217); ROC curve analysi; Three-zone classification |
| Description: |
Early and accurate diagnosis of Alzheimer's disease (AD) typically relies on invasive or expensive methods like cerebrospinal fluid (CSF) biomarkers and amyloid PET imaging. Blood-based biomarkers, particularly plasma phosphorylated tau (pTau181, pTau217) and amyloid-beta ratios (Aβ42/40), offer a more accessible diagnostic alternative. This study assessed the diagnostic accuracy of plasma biomarkers and developed a three-zone classification model to reduce reliance on invasive confirmatory tests. We retrospectively evaluated 109 participants referred to a tertiary memory clinic. Participants underwent cognitive assessments, brain MRI, CSF biomarker analyses (pTau181, Aβ42/40), and plasma biomarker measurements (pTau181, pTau217, Aβ42/40, pTau217/Aβ42 ratio). Diagnostic performance was evaluated using ROC analyses, and thresholds achieving ≥ 95 % sensitivity and specificity were used to define low, intermediate and high-risk zones. Plasma biomarkers correlated significantly with CSF biomarkers. For identifying AD pathology (A+/T + vs. others), plasma pTau217 and the pTau217/Aβ42 ratio demonstrated the highest accuracy (both AUC=0.95), outperforming plasma pTau181 (AUC=0.88) and Aβ42/40 ratio (AUC=0.73). At optimal thresholds, plasma pTau217 showed 87.5 % sensitivity and 93.4 % specificity, whereas the pTau217/Aβ42 ratio showed higher sensitivity (95.8 %) but lower specificity (85.2 %). Using the three-zone model, plasma pTau217 enabled definitive classification in 80.7 % of patients, increasing to 84.4 % with the pTau217/Aβ42 ratio. Among patients with mild cognitive impairment, plasma pTau217 achieved excellent accuracy (AUC=0.98). Plasma pTau217, alone or combined with Aβ42, provides highly accurate and scalable identification of AD pathology, substantially reducing the need for invasive diagnostic procedures. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| ISBN: |
978-0-19-745802-0; 0-19-745802-5 |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/41422686; info:eu-repo/semantics/altIdentifier/wos/WOS:001649250100001; volume:159; firstpage:60; lastpage:68; numberofpages:9; journal:NEUROBIOLOGY OF AGING; https://hdl.handle.net/11368/3122482; https://www.sciencedirect.com/science/article/pii/S0197458025002179?via=ihub |
| DOI: |
10.1016/j.neurobiolaging.2025.12.005 |
| Availability: |
https://hdl.handle.net/11368/3122482; https://doi.org/10.1016/j.neurobiolaging.2025.12.005; https://www.sciencedirect.com/science/article/pii/S0197458025002179?via=ihub |
| Rights: |
info:eu-repo/semantics/openAccess ; license:Creative commons ; license uri:http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Accession Number: |
edsbas.45135B3C |
| Database: |
BASE |