Comparative performance of plasma pTau181/Aβ42, pTau217/Aβ42 ratios, and individual measurements in detecting brain amyloidosis

Background: Early detection of brain amyloidosis (Aβ+) 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 underexp...

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Autores: Lehmann, Sylvain|||0000-0001-6117-562X, Gabelle, Audrey, Delaby, Constance|||0000-0002-8606-6814, Hirtz, Christophe, Mondesert, Etienne, Bennys, Karim, Duchiron, Marie, Busto, Germain, Morchikh, Mehdi, Cristol, Jean-Paul, Barnier-Figue, Genevieve, Perrein, Florence, Turpinat, Cédric, Jurici, Snejana
Tipo de recurso: artículo
Fecha de publicación:2025
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:325974
Acceso en línea:https://ddd.uab.cat/record/325974
https://dx.doi.org/urn:doi:10.1016/j.ebiom.2025.105805
Access Level:acceso abierto
Palabra clave:Alzheimer
Biomarkers
Blood
Diagnosis
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spelling Comparative performance of plasma pTau181/Aβ42, pTau217/Aβ42 ratios, and individual measurements in detecting brain amyloidosisLehmann, Sylvain|||0000-0001-6117-562XGabelle, AudreyDelaby, Constance|||0000-0002-8606-6814Hirtz, ChristopheMondesert, EtienneBennys, KarimDuchiron, MarieBusto, GermainMorchikh, MehdiCristol, Jean-PaulBarnier-Figue, GenevievePerrein, FlorenceTurpinat, CédricJurici, SnejanaAlzheimerBiomarkersBloodDiagnosisBackground: Early detection of brain amyloidosis (Aβ+) 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 Aβ42 ratios in detecting Aβ+ status. Methods: This study included 423 participants from the multicenter prospective ALZAN cohort, recruited for cognitive complaints. Aβ+ status was determined using cerebrospinal fluid (CSF) biomarkers. The confirmatory cohort comprises 1176 patient samples from the Alzheimer's Disease Neuroimaging Initiative (ADNI), with Aβ+ status determined by positron emission tomography (PET) imaging. Plasma biomarkers (pTau181, pTau217, Aβ40, Aβ42) were measured using immunoassays and mass spectrometry, with specific ratios calculated. In the ALZAN 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 Aβ+ status. Secondary outcomes in the ALZAN cohort included the proportion of patients classified as low, intermediate, or high risk for Aβ+ using a two-cutoff approach. Findings: In ALZAN the pTau181/Aβ42 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/Aβ42 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 Aβ+ status in individuals with early cognitive decline. Diagnostic accuracy of ratios vs. individual measurement was confirmed in the ADNI cohort. In ALZAN, using two-cutoff workflows with pTau217/Aβ42 instead of pTau217 alone reduced the intermediate-risk zone from ∼16% to ∼8%, enhancing stratification for clinical decision-making. Interpretation: The pTau217/Aβ42 ratio demonstrated improved diagnostic performance for detecting Aβ+ 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. Funding: Fondation Research Alzheimer (ALZAN projet), AXA Mécénat Santé (INTERVAL Project), Fondation pour la Recherche Médicale (FRM, team Proteinopathies).Universitat Autònoma de Barcelona. Departament de Medicina 22025-01-0120252025-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/325974https://dx.doi.org/urn:doi:10.1016/j.ebiom.2025.105805reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:3259742026-06-06T12:50:31Z
dc.title.none.fl_str_mv Comparative performance of plasma pTau181/Aβ42, pTau217/Aβ42 ratios, and individual measurements in detecting brain amyloidosis
title Comparative performance of plasma pTau181/Aβ42, pTau217/Aβ42 ratios, and individual measurements in detecting brain amyloidosis
spellingShingle Comparative performance of plasma pTau181/Aβ42, pTau217/Aβ42 ratios, and individual measurements in detecting brain amyloidosis
Lehmann, Sylvain|||0000-0001-6117-562X
Alzheimer
Biomarkers
Blood
Diagnosis
title_short Comparative performance of plasma pTau181/Aβ42, pTau217/Aβ42 ratios, and individual measurements in detecting brain amyloidosis
title_full Comparative performance of plasma pTau181/Aβ42, pTau217/Aβ42 ratios, and individual measurements in detecting brain amyloidosis
title_fullStr Comparative performance of plasma pTau181/Aβ42, pTau217/Aβ42 ratios, and individual measurements in detecting brain amyloidosis
title_full_unstemmed Comparative performance of plasma pTau181/Aβ42, pTau217/Aβ42 ratios, and individual measurements in detecting brain amyloidosis
title_sort Comparative performance of plasma pTau181/Aβ42, pTau217/Aβ42 ratios, and individual measurements in detecting brain amyloidosis
dc.creator.none.fl_str_mv Lehmann, Sylvain|||0000-0001-6117-562X
Gabelle, Audrey
Delaby, Constance|||0000-0002-8606-6814
Hirtz, Christophe
Mondesert, Etienne
Bennys, Karim
Duchiron, Marie
Busto, Germain
Morchikh, Mehdi
Cristol, Jean-Paul
Barnier-Figue, Genevieve
Perrein, Florence
Turpinat, Cédric
Jurici, Snejana
author Lehmann, Sylvain|||0000-0001-6117-562X
author_facet Lehmann, Sylvain|||0000-0001-6117-562X
Gabelle, Audrey
Delaby, Constance|||0000-0002-8606-6814
Hirtz, Christophe
Mondesert, Etienne
Bennys, Karim
Duchiron, Marie
Busto, Germain
Morchikh, Mehdi
Cristol, Jean-Paul
Barnier-Figue, Genevieve
Perrein, Florence
Turpinat, Cédric
Jurici, Snejana
author_role author
author2 Gabelle, Audrey
Delaby, Constance|||0000-0002-8606-6814
Hirtz, Christophe
Mondesert, Etienne
Bennys, Karim
Duchiron, Marie
Busto, Germain
Morchikh, Mehdi
Cristol, Jean-Paul
Barnier-Figue, Genevieve
Perrein, Florence
Turpinat, Cédric
Jurici, Snejana
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universitat Autònoma de Barcelona. Departament de Medicina
dc.subject.none.fl_str_mv Alzheimer
Biomarkers
Blood
Diagnosis
topic Alzheimer
Biomarkers
Blood
Diagnosis
description Background: Early detection of brain amyloidosis (Aβ+) 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 Aβ42 ratios in detecting Aβ+ status. Methods: This study included 423 participants from the multicenter prospective ALZAN cohort, recruited for cognitive complaints. Aβ+ status was determined using cerebrospinal fluid (CSF) biomarkers. The confirmatory cohort comprises 1176 patient samples from the Alzheimer's Disease Neuroimaging Initiative (ADNI), with Aβ+ status determined by positron emission tomography (PET) imaging. Plasma biomarkers (pTau181, pTau217, Aβ40, Aβ42) were measured using immunoassays and mass spectrometry, with specific ratios calculated. In the ALZAN 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 Aβ+ status. Secondary outcomes in the ALZAN cohort included the proportion of patients classified as low, intermediate, or high risk for Aβ+ using a two-cutoff approach. Findings: In ALZAN the pTau181/Aβ42 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/Aβ42 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 Aβ+ status in individuals with early cognitive decline. Diagnostic accuracy of ratios vs. individual measurement was confirmed in the ADNI cohort. In ALZAN, using two-cutoff workflows with pTau217/Aβ42 instead of pTau217 alone reduced the intermediate-risk zone from ∼16% to ∼8%, enhancing stratification for clinical decision-making. Interpretation: The pTau217/Aβ42 ratio demonstrated improved diagnostic performance for detecting Aβ+ 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. Funding: Fondation Research Alzheimer (ALZAN projet), AXA Mécénat Santé (INTERVAL Project), Fondation pour la Recherche Médicale (FRM, team Proteinopathies).
publishDate 2025
dc.date.none.fl_str_mv 2
2025-01-01
2025
2025-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
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format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/325974
https://dx.doi.org/urn:doi:10.1016/j.ebiom.2025.105805
url https://ddd.uab.cat/record/325974
https://dx.doi.org/urn:doi:10.1016/j.ebiom.2025.105805
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
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dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
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instname:Universitat Autònoma de Barcelona
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