Diagnostic performance of plasma pTau217, pTau181, Aß1-42 and Aß1-40 in the LUMIPULSE automated platform for the detection of Alzheimer disease
Por:
Arranz, J, Zhu, NL, Rubio-Guerra, S, Rodríguez-Baz, I, Ferrer, R, Carmona-Iragui, M, Barroeta, I, Illan-Gala, I, Santos-Santos, M, Fortea, J, Lleó, A, Tondo, M, Alcolea, D
Publicada:
26 jun 2024
Resumen:
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.
Filiaciones:
Arranz, J:
Hosp La Santa Creu & St Pau, Dept Neurol, St Pau Memory Unit, IR SANT PAU, C St Quinti 89, Barcelona 08041, Spain
Hosp La Santa Creu & St Pau, IR SANT PAU, Dept Neurol, Unidad Alzheimer Down, Barcelona, Spain
Barcelona Med Ctr, Fundacio Catalana Sindrome, Barcelona, Spain
Univ Autonoma Barcelona, Barcelona, Spain
Zhu, NL:
Hosp La Santa Creu & St Pau, Dept Neurol, St Pau Memory Unit, IR SANT PAU, C St Quinti 89, Barcelona 08041, Spain
Univ Autonoma Barcelona, Barcelona, Spain
CIBERNED, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Rubio-Guerra, S:
Hosp La Santa Creu & St Pau, Dept Neurol, St Pau Memory Unit, IR SANT PAU, C St Quinti 89, Barcelona 08041, Spain
Univ Autonoma Barcelona, Barcelona, Spain
Rodríguez-Baz, I:
Hosp La Santa Creu & St Pau, Dept Neurol, St Pau Memory Unit, IR SANT PAU, C St Quinti 89, Barcelona 08041, Spain
Hosp La Santa Creu & St Pau, IR SANT PAU, Dept Neurol, Unidad Alzheimer Down, Barcelona, Spain
Barcelona Med Ctr, Fundacio Catalana Sindrome, Barcelona, Spain
Ferrer, R:
Univ Autonoma Barcelona, Hosp La Santa Creu & St Pau, Serv Bioquim & Biol Mol, IR SANT PAU, C St Quinti 89, Barcelona 08041, Spain
Carmona-Iragui, M:
Hosp La Santa Creu & St Pau, Dept Neurol, St Pau Memory Unit, IR SANT PAU, C St Quinti 89, Barcelona 08041, Spain
Hosp La Santa Creu & St Pau, IR SANT PAU, Dept Neurol, Unidad Alzheimer Down, Barcelona, Spain
Barcelona Med Ctr, Fundacio Catalana Sindrome, Barcelona, Spain
CIBERNED, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Barroeta, I:
Hosp La Santa Creu & St Pau, Dept Neurol, St Pau Memory Unit, IR SANT PAU, C St Quinti 89, Barcelona 08041, Spain
Hosp La Santa Creu & St Pau, IR SANT PAU, Dept Neurol, Unidad Alzheimer Down, Barcelona, Spain
Barcelona Med Ctr, Fundacio Catalana Sindrome, Barcelona, Spain
CIBERNED, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Illan-Gala, I:
Hosp La Santa Creu & St Pau, Dept Neurol, St Pau Memory Unit, IR SANT PAU, C St Quinti 89, Barcelona 08041, Spain
CIBERNED, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Santos-Santos, M:
Hosp La Santa Creu & St Pau, Dept Neurol, St Pau Memory Unit, IR SANT PAU, C St Quinti 89, Barcelona 08041, Spain
CIBERNED, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Fortea, J:
Hosp La Santa Creu & St Pau, Dept Neurol, St Pau Memory Unit, IR SANT PAU, C St Quinti 89, Barcelona 08041, Spain
Hosp La Santa Creu & St Pau, IR SANT PAU, Dept Neurol, Unidad Alzheimer Down, Barcelona, Spain
Barcelona Med Ctr, Fundacio Catalana Sindrome, Barcelona, Spain
CIBERNED, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Lleó, A:
Hosp La Santa Creu & St Pau, Dept Neurol, St Pau Memory Unit, IR SANT PAU, C St Quinti 89, Barcelona 08041, Spain
CIBERNED, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Tondo, M:
Univ Autonoma Barcelona, Hosp La Santa Creu & St Pau, Serv Bioquim & Biol Mol, IR SANT PAU, C St Quinti 89, Barcelona 08041, Spain
CIBERDEM, Ctr Invest Biomed Red Diabet & Enfermedades Metab, Madrid, Spain
Alcolea, D:
Hosp La Santa Creu & St Pau, Dept Neurol, St Pau Memory Unit, IR SANT PAU, C St Quinti 89, Barcelona 08041, Spain
CIBERNED, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Green Published, gold
|