Diagnostic performance of plasma pTau<sub>217</sub>, pTau<sub>181</sub>, Aß<sub>1-42</sub> and Aß<sub>1-40</sub> in the LUMIPULSE automated platform for the detection of Alzheimer disease
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 fro...
| Autores: | , , , , , , , , , , , , |
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| Tipo de documento: | artigo |
| Estado: | Versão publicada |
| Data de publicação: | 2024 |
| País: | España |
| Recursos: | Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau) |
| Repositório: | r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau |
| OAI Identifier: | oai:iibsantpau.fundanetsuite.com:p18004 |
| Acesso em linha: | https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=18004 https://ddd.uab.cat/record/324173 |
| Access Level: | Acceso aberto |
| Palavra-chave: | Plasma Biomarkers Alzheimer Blood Amyloid Tau |
| Resumo: | 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 A beta(1-42)/A beta(1-40) ratio. Plasma pTau(217), pTau(181), A beta(1-42) and A beta(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 A beta(1-42)/A beta(1-40) ratio. We analyzed the concordance of pTau(217) with CSF amyloidosis. Results Plasma pTau(217) and pTau(181) concentration were higher in A + than A- while the plasma A beta(1-42)/A beta(1-40) ratio was lower in A + compared to A-. pTau(181) and the A beta(1-42)/A beta(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 A beta(1-42)/A beta(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 (x 3.2) 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. |
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