Comparative performance of plasma pTau181/Aß42 , pTau217/Aß42 ratios, and individual measurements in detecting brain amyloidosis
Por:
Lehmann, S, Gabelle, A, Duchiron, M, Busto, G, Morchikh, M, Delaby, C, Hirtz, C, Mondesert, E, Cristol, JP, Barnier-Figue, G, Perrein, F, Jurici, S, Bennys, K
Publicada:
1 jul 2025
Ahead of Print:
1 jun 2025
Resumen:
Background Early detection of brain amyloidosis (A beta+) is crucial for diagnosing Alzheimer' disease (AD) and optimizing patient management, especially in light of emerging treatments. While plasma biomarkers are promising, their combined diagnostic value through specific ratios remains underexplored. In this study, we assess the diagnostic accuracy of plasma pTau isoform (pTau181 and pTau217) to A beta 42 ratios in detecting A beta+ status. Methods This study included 423 participants from the multicenter prospective ALLAN cohort, recruited for cognitive complaints. A beta+ status was determined using cerebrospinal fluid (CSF) biomarkers. The confirmatory cohort comprises 1176 patient samples from the Alzheimer's Disease Neuroimaging Initiative (ADNI), with A beta+ status determined by positron emission tomography (PET) imaging. Plasma biomarkers (pTau181, pTau217, A beta 40, A beta 42) were measured using immunoassays and mass spectrometry, with specific ratios calculated. In the ALLAN cohort, the impact of confounding factors such as age, renal function, ApoE 4 status, body mass index, and the delay between blood collection and processing was also evaluated to assess their influence on biomarker concentrations and diagnostic performance. The primary outcome was the diagnostic performance of plasma biomarkers and their ratios for detecting A beta+ status. Secondary outcomes in the ALLAN cohort included the proportion of patients classified as low, intermediate, or high risk for A beta+ using a two-cutoff approach. Findings In ALLAN the pTau181/A beta 42 ratio matched the diagnostic performance of pTau217 (AUC of 0.911 (0.882-0.940) vs. 0.909 (0.879-0.939), P = 0.85). The pTau217/A beta 42 ratio demonstrated the highest diagnostic accuracy, with an AUC of 0.927 (0.900-0.954). Both ratios effectively mitigated confounding factors, such as variations in renal function, and were also efficient in identifying A beta+ status in individuals with early cognitive decline. Diagnostic accuracy of ratios vs. individual measurement was confirmed in the ADNI cohort. In ALLAN, using two-cutoff workflows with pTau217/A beta 42 instead of pTau217 alone reduced the intermediate-risk zone from-16% to-8%, enhancing stratification for clinical decision-making. Interpretation The pTau217/A beta 42 ratio demonstrated improved diagnostic performance for detecting A beta+ compared to individual biomarkers, potentially reducing diagnostic uncertainty. These findings suggest that plasma biomarker ratios could be useful; however, further validation in independent and diverse clinical settings is necessary before broader clinical implementation. Copyright (c) 2025 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Filiaciones:
Lehmann, S:
Univ Montpellier, LBPC PPC, INM INSERM, IRMB CHU Montpellier, Montpellier, France
Gabelle, A:
Univ Montpellier, Memory Res & Resources Ctr, Dept Neurol, Inserm,INM,NeuroPEPs Team, F-34000 Montpellier, France
Duchiron, M:
Univ Montpellier, LBPC PPC, INM INSERM, IRMB CHU Montpellier, Montpellier, France
Busto, G:
Univ Montpellier, Memory Res & Resources Ctr, Dept Neurol, Inserm,INM,NeuroPEPs Team, F-34000 Montpellier, France
Morchikh, M:
Univ Montpellier, LBPC PPC, INM INSERM, IRMB CHU Montpellier, Montpellier, France
Delaby, C:
Univ Montpellier, LBPC PPC, INM INSERM, IRMB CHU Montpellier, Montpellier, France
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Biomed Res Inst St Pau, St Pau Memory Unit, Barcelona, Spain
Hirtz, C:
Univ Montpellier, LBPC PPC, INM INSERM, IRMB CHU Montpellier, Montpellier, France
Mondesert, E:
Univ Montpellier, LBPC PPC, INM INSERM, IRMB CHU Montpellier, Montpellier, France
Hop Lapeyronie, Serv Biochim, CHU Montpellier, Montpellier, France
Cristol, JP:
Hop Lapeyronie, Serv Biochim, CHU Montpellier, Montpellier, France
Barnier-Figue, G:
Perpignan CH, Perpignan, France
Perrein, F:
CHU Nimes, Neurol, Nimes, France
Jurici, S:
Perpignan CH, Perpignan, France
Bennys, K:
Univ Montpellier, Memory Res & Resources Ctr, Dept Neurol, Inserm,INM,NeuroPEPs Team, F-34000 Montpellier, France
Green Submitted, gold
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