Exploring the ability of plasma pTau217, pTau181 and beta-amyloid in mirroring cerebrospinal fluid biomarker profile of Mild Cognitive Impairment by the fully automated Lumipulse® platform

Abstract Background The approval of new disease-modifying therapies by the U.S. Food and Drug Administration and the European Medicine Agency makes it necessary to optimize non-invasive and cost-effective tools for the identification of subjects at-risk of developing Alzheimer’s Disease (AD). Plasma...

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Main Authors: Marcella Catania, Claudia Battipaglia, Alberto Perego, Erika Salvi, Emanuela Maderna, Federico Angelo Cazzaniga, Paolo M. Rossini, Camillo Marra, Nicola Vanacore, Alberto Redolfi, Daniela Perani, Patrizia Spadin, Maria Cotelli, Stefano Cappa, Naike Caraglia, Pietro Tiraboschi, Fabrizio Tagliavini, Giuseppe Di Fede
Format: Article
Language:English
Published: BMC 2025-01-01
Series:Fluids and Barriers of the CNS
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Online Access:https://doi.org/10.1186/s12987-025-00620-5
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author Marcella Catania
Claudia Battipaglia
Alberto Perego
Erika Salvi
Emanuela Maderna
Federico Angelo Cazzaniga
Paolo M. Rossini
Camillo Marra
Nicola Vanacore
Alberto Redolfi
Daniela Perani
Patrizia Spadin
Maria Cotelli
Stefano Cappa
Naike Caraglia
Pietro Tiraboschi
Fabrizio Tagliavini
Giuseppe Di Fede
author_facet Marcella Catania
Claudia Battipaglia
Alberto Perego
Erika Salvi
Emanuela Maderna
Federico Angelo Cazzaniga
Paolo M. Rossini
Camillo Marra
Nicola Vanacore
Alberto Redolfi
Daniela Perani
Patrizia Spadin
Maria Cotelli
Stefano Cappa
Naike Caraglia
Pietro Tiraboschi
Fabrizio Tagliavini
Giuseppe Di Fede
author_sort Marcella Catania
collection DOAJ
description Abstract Background The approval of new disease-modifying therapies by the U.S. Food and Drug Administration and the European Medicine Agency makes it necessary to optimize non-invasive and cost-effective tools for the identification of subjects at-risk of developing Alzheimer’s Disease (AD). Plasma biomarkers are excellent candidates. However, their ability to reflect the cerebrospinal fluid (CSF) profile - that remains to date the gold standard for the biochemical diagnosis of AD - needs to be confirmed and validated before their implementation in clinical practice. The aims of this study are to analyse the correlation between CSF and plasma Aβ40, Aβ42, Aβ42/Aβ40 and pTau181, and to assess the diagnostic performance of plasma biomarkers in a cohort of subjects affected by Mild Cognitive Impairment (MCI). Methods The study was performed on 306 subjects affected by MCI, enrolled in the context of the Italian Interceptor Project. Aβ40, Aβ42 and pTau181 were analysed in plasma and CSF, and pTau217 was measured in plasma. The fully automated chemiluminescence enzyme immunoassay and the Lumipulse® G600II (Fujirebio) instrument were used for all measurements. We analysed the correlations between CSF and plasma biomarkers and the differences of plasma biomarker concentrations after grouping MCI cases according to AT classification of CSF AD biomarker profiles. Results We found statistically significant positive correlations between CSF and plasma Aβ42, Aβ42/Aβ40 ratio and pTau181. All the biomarkers, except Aβ40, showed differences in A+ vs. A-, A+T+ vs. A-T- and A+T- vs. A-T- patients. Moreover, Aβ42 and Aβ42/Aβ40 plasma levels were lower in A+T- compared to A-T- and A-T+ groups, and pTau181 and pTau217 plasma levels were higher in A+T+ compared to A+T-. Aβ42/Aβ40 and pTau217 showed a robust performance in distinguishing A+ from A- (AUC = 0.857 and 0.862, respectively) and A+T+ from A-T- (AUC = 0.866 and 0.911) subjects. Conclusions Our results suggest that plasma biomarkers, and especially Aβ42/Aβ40 ratio and pTau217, are promising candidates for the early detection of AD pathology.
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series Fluids and Barriers of the CNS
spelling doaj-art-32fa7b1b7d9e4e62919372cc6456d0f62025-01-26T12:48:29ZengBMCFluids and Barriers of the CNS2045-81182025-01-0122111110.1186/s12987-025-00620-5Exploring the ability of plasma pTau217, pTau181 and beta-amyloid in mirroring cerebrospinal fluid biomarker profile of Mild Cognitive Impairment by the fully automated Lumipulse® platformMarcella Catania0Claudia Battipaglia1Alberto Perego2Erika Salvi3Emanuela Maderna4Federico Angelo Cazzaniga5Paolo M. Rossini6Camillo Marra7Nicola Vanacore8Alberto Redolfi9Daniela Perani10Patrizia Spadin11Maria Cotelli12Stefano Cappa13Naike Caraglia14Pietro Tiraboschi15Fabrizio Tagliavini16Giuseppe Di Fede17Neurology 5 - Neuropathology Unit, Fondazione IRCCS – Istituto Neurologico Carlo BestaNeurology 5 - Neuropathology Unit, Fondazione IRCCS – Istituto Neurologico Carlo BestaFujirebio Italia S.r.lComputational multi-Omics of Neurological Disorders (MIND) Lab and Data Science Center, Fondazione IRCCS – Istituto Neurologico Carlo BestaNeurology 5 - Neuropathology Unit, Fondazione IRCCS – Istituto Neurologico Carlo BestaNeurology 5 - Neuropathology Unit, Fondazione IRCCS – Istituto Neurologico Carlo BestaDepartment of Neuroscience & Neurorehabilitation, IRCCS San Raffaele RomaNeurology Unit, Fondazione Policlinico Universitario “A. Gemelli” IRCCSNational Center for Disease Prevention and Health Promotion, National Institute of HealthLaboratory of Neuroinformatics, IRCCS Istituto Centro San Giovanni di Dio FatebenefratelliNuclear Medicine Unit, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific InstituteAssociazione Italiana Malattia di Alzheimer - AIMAIRCCS Istituto Centro San Giovanni di Dio FatebenefratelliUniversity Institute of Advanced StudiesMemory Clinic, Fondazione Policlinico Universitario “A. Gemelli” IRCCSNeurology 5 - Neuropathology Unit, Fondazione IRCCS – Istituto Neurologico Carlo BestaFondazione IRCCS Istituto Neurologico Carlo BestaNeurology 5 - Neuropathology Unit, Fondazione IRCCS – Istituto Neurologico Carlo BestaAbstract Background The approval of new disease-modifying therapies by the U.S. Food and Drug Administration and the European Medicine Agency makes it necessary to optimize non-invasive and cost-effective tools for the identification of subjects at-risk of developing Alzheimer’s Disease (AD). Plasma biomarkers are excellent candidates. However, their ability to reflect the cerebrospinal fluid (CSF) profile - that remains to date the gold standard for the biochemical diagnosis of AD - needs to be confirmed and validated before their implementation in clinical practice. The aims of this study are to analyse the correlation between CSF and plasma Aβ40, Aβ42, Aβ42/Aβ40 and pTau181, and to assess the diagnostic performance of plasma biomarkers in a cohort of subjects affected by Mild Cognitive Impairment (MCI). Methods The study was performed on 306 subjects affected by MCI, enrolled in the context of the Italian Interceptor Project. Aβ40, Aβ42 and pTau181 were analysed in plasma and CSF, and pTau217 was measured in plasma. The fully automated chemiluminescence enzyme immunoassay and the Lumipulse® G600II (Fujirebio) instrument were used for all measurements. We analysed the correlations between CSF and plasma biomarkers and the differences of plasma biomarker concentrations after grouping MCI cases according to AT classification of CSF AD biomarker profiles. Results We found statistically significant positive correlations between CSF and plasma Aβ42, Aβ42/Aβ40 ratio and pTau181. All the biomarkers, except Aβ40, showed differences in A+ vs. A-, A+T+ vs. A-T- and A+T- vs. A-T- patients. Moreover, Aβ42 and Aβ42/Aβ40 plasma levels were lower in A+T- compared to A-T- and A-T+ groups, and pTau181 and pTau217 plasma levels were higher in A+T+ compared to A+T-. Aβ42/Aβ40 and pTau217 showed a robust performance in distinguishing A+ from A- (AUC = 0.857 and 0.862, respectively) and A+T+ from A-T- (AUC = 0.866 and 0.911) subjects. Conclusions Our results suggest that plasma biomarkers, and especially Aβ42/Aβ40 ratio and pTau217, are promising candidates for the early detection of AD pathology.https://doi.org/10.1186/s12987-025-00620-5Alzheimer’s diseaseMild Cognitive ImpairmentCSFPlasmaBiomarkersDiagnosis
spellingShingle Marcella Catania
Claudia Battipaglia
Alberto Perego
Erika Salvi
Emanuela Maderna
Federico Angelo Cazzaniga
Paolo M. Rossini
Camillo Marra
Nicola Vanacore
Alberto Redolfi
Daniela Perani
Patrizia Spadin
Maria Cotelli
Stefano Cappa
Naike Caraglia
Pietro Tiraboschi
Fabrizio Tagliavini
Giuseppe Di Fede
Exploring the ability of plasma pTau217, pTau181 and beta-amyloid in mirroring cerebrospinal fluid biomarker profile of Mild Cognitive Impairment by the fully automated Lumipulse® platform
Fluids and Barriers of the CNS
Alzheimer’s disease
Mild Cognitive Impairment
CSF
Plasma
Biomarkers
Diagnosis
title Exploring the ability of plasma pTau217, pTau181 and beta-amyloid in mirroring cerebrospinal fluid biomarker profile of Mild Cognitive Impairment by the fully automated Lumipulse® platform
title_full Exploring the ability of plasma pTau217, pTau181 and beta-amyloid in mirroring cerebrospinal fluid biomarker profile of Mild Cognitive Impairment by the fully automated Lumipulse® platform
title_fullStr Exploring the ability of plasma pTau217, pTau181 and beta-amyloid in mirroring cerebrospinal fluid biomarker profile of Mild Cognitive Impairment by the fully automated Lumipulse® platform
title_full_unstemmed Exploring the ability of plasma pTau217, pTau181 and beta-amyloid in mirroring cerebrospinal fluid biomarker profile of Mild Cognitive Impairment by the fully automated Lumipulse® platform
title_short Exploring the ability of plasma pTau217, pTau181 and beta-amyloid in mirroring cerebrospinal fluid biomarker profile of Mild Cognitive Impairment by the fully automated Lumipulse® platform
title_sort exploring the ability of plasma ptau217 ptau181 and beta amyloid in mirroring cerebrospinal fluid biomarker profile of mild cognitive impairment by the fully automated lumipulse r platform
topic Alzheimer’s disease
Mild Cognitive Impairment
CSF
Plasma
Biomarkers
Diagnosis
url https://doi.org/10.1186/s12987-025-00620-5
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