Diagnostic performance of plasma pTau 217, pTau 181, Aβ 1-42 and Aβ 1-40 in the LUMIPULSE automated platform for the detection of Alzheimer disease.

Autor: Arranz J; IR SANT PAU, Hospital de la Santa Creu i Sant Pau., Zhu N; IR SANT PAU, Hospital de la Santa Creu i Sant Pau., Rubio-Guerra S; IR SANT PAU, Hospital de la Santa Creu i Sant Pau., Rodríguez-Baz Í; IR SANT PAU, Hospital de la Santa Creu i Sant Pau., Ferrer R; IR SANT PAU, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona., Carmona-Iragui M; IR SANT PAU, Hospital de la Santa Creu i Sant Pau., Barroeta I; IR SANT PAU, Hospital de la Santa Creu i Sant Pau., Illán-Gala I; IR SANT PAU, Hospital de la Santa Creu i Sant Pau., Santos-Santos M; IR SANT PAU, Hospital de la Santa Creu i Sant Pau., Fortea J; IR SANT PAU, Hospital de la Santa Creu i Sant Pau., Lleó A; IR SANT PAU, Hospital de la Santa Creu i Sant Pau., Tondo M; IR SANT PAU, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona., Alcolea D; IR SANT PAU, Hospital de la Santa Creu i Sant Pau.
Jazyk: angličtina
Zdroj: Research square [Res Sq] 2023 Dec 13. Date of Electronic Publication: 2023 Dec 13.
DOI: 10.21203/rs.3.rs-3725688/v1
Abstrakt: Background: Recently developed blood markers for Alzheimer's disease (AD) detection have high accuracy but usually require ultra-sensitive analytic tools not commonly available in clinical laboratories, and their performance in clinical practice is unknown.
Methods: We analyzed plasma samples from 290 consecutive participants that underwent lumbar puncture in routine clinical practice in a specialized memory clinic (66 cognitively unimpaired, 130 participants with mild cognitive impairment, and 94 with dementia). Participants were classified as amyloid positive (A+) or negative (A-) according to CSF Aβ 1-42 /Aβ 1-40 ratio. Plasma pTau 217 , pTau 181 , Aβ 1-42 and Aβ 1-40 were measured in the fully-automated LUMIPULSE platform. We used linear regression to compare plasma biomarkers concentrations between A + and A- groups, evaluated Spearman's correlation between plasma and CSF and performed ROC analyses to assess their diagnostic accuracy to detect brain amyloidosis as determined by CSF Aβ 1-42 /Aβ 1-40 ratio. We analyzed the potential of pTau 217 to predict amyloidosis in CSF.
Results: Plasma pTau 217 and pTau 181 concentration were higher in A + than A- while the plasma Aβ 1-42 /Aβ 1-40 ratio was lower in A + compared to A-. pTau 181 and the Aβ 1-42 /Aβ 1-40 ratio showed moderate correlation between plasma and CSF (Rho = 0.66 and 0.69, respectively). The areas under the ROC curve to discriminate A + from A- participants were 0.94 (95% CI 0.92-0.97) for pTau 217 , and 0.88 (95% CI 0.84-0.92) for both pTau 181 and Aβ 1-42 /Aβ 1-40 . Chronic kidney disease (CKD) was related to increased plasma biomarker concentrations, but ratios were less affected. Plasma pTau 217 had the highest fold change (x4.2) and showed high predictive capability in discriminating A + from A-, having 4-7% misclassification rate. The global accuracy of plasma pTau 217 using a two-threshold approach was robust in symptomatic groups, exceeding 90%.
Conclusion: The evaluation of blood biomarkers on an automated platform exhibited high diagnostic accuracy for AD pathophysiology, and pTau 217 showed excellent diagnostic accuracy to identify participants with AD in a consecutive sample representing the routine clinical practice in a specialized memory unit.
Competing Interests: Competing interests Daniel Alcolea is employed by Hospital de la Santa Creu i Sant Pau and received research grants from Pla Estratègic de Recerca i Innovació en Salut (PERIS SLT006/17/125), and from Instituto de Salud Carlos III (PI18/00435 and INT19/00016). He participated in advisory boards from Fujirebio-Europe and Roche Diagnostics and received speaker honoraria from Fujirebio-Europe, Roche Diagnostics, Nutricia, Zambon S.A.U., Esteve, and from Krka Farmacéutica S.L. Javier Arranz is employed by Biomedical Research Institute Sant Pau. He is funded by a “Rio Hortega” research grant from the Institute of Health Carlos III. Declarations of interest: none Nuole Zhu is employed by Biomedical Research Institute Sant Pau. He is funded by a “Rio Hortega” research grant from the Institute of Health Carlos III. Declarations of interest: none Sara Rubio-Guerra is employed by Hospital de la Santa Creu i Sant Pau. Declarations of interest: none Iñigo Rodríguez-Baz is employed by Biomedical Research Institute Sant Pau. He is funded by a “Rio Hortega” research grant from the Institute of Health Carlos III. Declarations of interest: none. Rosa Ferrer is employed by Hospital de la Santa Creu i Sant Pau. Declarations of interest: none María Carmona-Iragui is employed by Hospital de la Santa Creu i Sant Pau. Declarations of interest: none. Isabel Barroeta is employed by Hospital de la Santa Creu i Sant Pau. Declarations of interest: none. Dr. Illán-Gala is a senior Atlantic Fellows for Equity in Brain Health at the Global Brain Health Institute (GBHI), and is supported with funding from GBHI, Alzheimer’s Association, and Alzheimer’s Society (GBHI ALZ UK-21-720973 and AACSF-21-850193). Dr Illán-Gala was also supported by the Juan Rodés Contract (JR20/0018) and Fondo de Investigaciones Sanitario, (PI21/00791) from Instituto de Salud Carlos III. Ignacio Illán-Gala reported receiving personal fees from Nutricia, Esteve, UCB, and Neuraxpharm Spain outside the submitted work. Miguel Santos-Santos is employed by Hospital de la Santa Creu i Sant Pau. His research is supported by funding from the Spanish Institute of Health Carlos III (Juan Rodés contract JR18-00018; Fondo de investigación sanitaria grant PI19/00882), the Alzheimer’s Association clinician scientist fellowship (AACSF-22-972945), and the National Institutes of Health (R01AG080470). Juan Fortea is employed by Hospital de la Santa Creu i Sant Pau and received research grants from Institute of Health Carlos III, National Institutes of Health, Fundació La Marató de TV3, and Pla Estratègic de Recerca i Innovació en Salut (PERIS). Dr. Fortea has served as a consultant for Novartis and Lundbeck, has received honoraria for lectures from Roche, NovoNordisk, Esteve and Biogen and served at advisory boards for AC Immune, Zambon and Lundbeck. Alberto Lleó is employed by Hospital de la Santa Creu i Sant Pau and received research grants from CIBERNED, Institute of Health Carlos III, Generalitat de Catalunya (PERIS and AGAUR) and Fundación Tatiana and BBVA. He participated in advisory boards from Biogen, Eisai, Fujirebio-Europe, Novartis, NovoNordisk, Nutricia, Otsuka Pharmaceutical, and Zambón, and received speaker honoraria from Lilly, Biogen, KRKA and Zambon. Mireia Tondo is employed by Hospital de la Santa Creu i Sant Pau and has received research grants from Instituto de Salud Carlos III (PI18/00164; PI21/00140) and has served as consultant in Araclon. Additional Declarations: Competing interest reported. Daniel Alcolea is employed by Hospital de la Santa Creu i Sant Pau and received research grants from Pla Estratègic de Recerca i Innovació en Salut (PERIS SLT006/17/125), and from Instituto de Salud Carlos III (PI18/00435 and INT19/00016). He participated in advisory boards from Fujirebio-Europe and Roche Diagnostics and received speaker honoraria from Fujirebio-Europe, Roche Diagnostics, Nutricia, Zambon S.A.U., Esteve, and from Krka Farmacéutica S.L. Javier Arranz is employed by Biomedical Research Institute Sant Pau. He is funded by a “Rio Hortega” research grant from the Institute of Health Carlos III. Declarations of interest: none Nuole Zhu is employed by Biomedical Research Institute Sant Pau. He is funded by a “Rio Hortega” research grant from the Institute of Health Carlos III. Declarations of interest: none Sara Rubio-Guerra is employed by Hospital de la Santa Creu i Sant Pau. Declarations of interest: none Iñigo Rodríguez-Baz is employed by Biomedical Research Institute Sant Pau. He is funded by a “Rio Hortega” research grant from the Institute of Health Carlos III. Declarations of interest: none. Rosa Ferrer is employed by Hospital de la Santa Creu i Sant Pau. Declarations of interest: none María Carmona-Iragui is employed by Hospital de la Santa Creu i Sant Pau. Declarations of interest: none. Isabel Barroeta is employed by Hospital de la Santa Creu i Sant Pau. Declarations of interest: none. Dr. Illán-Gala is a senior Atlantic Fellows for Equity in Brain Health at the Global Brain Health Institute (GBHI), and is supported with funding from GBHI, Alzheimer’s Association, and Alzheimer’s Society (GBHI ALZ UK-21-720973 and AACSF-21-850193). Dr Illán-Gala was also supported by the Juan Rodés Contract (JR20/0018) and Fondo de Investigaciones Sanitario, (PI21/00791) from Instituto de Salud Carlos III. Ignacio Illán-Gala reported receiving personal fees from Nutricia, Esteve, UCB, and Neuraxpharm Spain outside the submitted work. Miguel Santos-Santos is employed by Hospital de la Santa Creu i Sant Pau. His research is supported by funding from the Spanish Institute of Health Carlos III (Juan Rodés contract JR18-00018; Fondo de investigación sanitaria grant PI19/00882), the Alzheimer’s Association clinician scientist fellowship (AACSF-22-972945), and the National Institutes of Health (R01AG080470). Juan Fortea is employed by Hospital de la Santa Creu i Sant Pau and received research grants from Institute of Health Carlos III, National Institutes of Health, Fundació La Marató de TV3, and Pla Estratègic de Recerca i Innovació en Salut (PERIS). Dr. Fortea has served as a consultant for Novartis and Lundbeck, has received honoraria for lectures from Roche, NovoNordisk, Esteve and Biogen and served at advisory boards for AC Immune, Zambon and Lundbeck. Alberto Lleó is employed by Hospital de la Santa Creu i Sant Pau and received research grants from CIBERNED, Institute of Health Carlos III, Generalitat de Catalunya (PERIS and AGAUR) and Fundación Tatiana and BBVA. He participated in advisory boards from Biogen, Eisai, Fujirebio-Europe, Novartis, NovoNordisk, Nutricia, Otsuka Pharmaceutical, and Zambón, and received speaker honoraria from Lilly, Biogen, KRKA and Zambon. Mireia Tondo is employed by Hospital de la Santa Creu i Sant Pau and has received research grants from Instituto de Salud Carlos III (PI18/00164; PI21/00140) and has served as consultant in Araclon.
Databáze: MEDLINE
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