Clinical value of plasma pTau181 to predict Alzheimer's ' s disease pathology in a large real-world cohort of a memory clinic
Por:
Cano, A, Capdevila, M, Puerta, R, Arranz, J, Montrreal, L, de Rojas, I, García-González, P, Olivé, C, García-Gutiérrez, F, Sotolongo-Grau, O, Orellana, A, Aguilera, N, Ramis, M, Rosende-Roca, M, Lleó, A, Fortea, J, Tartari, JP, Lafuente, A, Vargas, L, Pérez-Cordón, A, Muñoz, N, Sanabria, A, Alegret, M, Morató, X, Tárraga, L, Fernández, V, Marquié, M, Valero, S, Alcolea, D, Boada, M, Ruiz, A
Publicada:
1 oct 2024
Ahead of Print:
1 sep 2024
Resumen:
Background: The identification of patients with an elevated risk of developing Alzheimer's disease (AD) dementia and eligible for the disease-modifying treatments (DMTs) in the earliest stages is one of the greatest challenges in the clinical practice. Plasma biomarkers has the potential to predict these issues, but further research is still needed to translate them to clinical practice. Here we evaluated the clinical applicability of plasma pTau181 as a predictive marker of AD pathology in a large real-world cohort of a memory clinic. Methods: Three independent cohorts (modelling [n = 991, 59.7% female], testing [n = 642, 56.2% female] and validation [n = 441, 55.1% female]) of real-world patients with subjective cognitive decline (SCD), mild cognitive impairment (MCI), AD dementia, and other dementias were included. Paired cerebrospinal fluid (CSF) and plasma samples were used to measure AT(N) CSF biomarkers and plasma pTau181. Findings: CSF and plasma pTau181 showed correlation in all phenotypes except in SCD and other dementias. Age significantly influenced the biomarker's performance. The general A beta(+) vs A beta(-) ROC curve showed an AUC = 0.77 [0.74-0.80], whereas the specific ROC curve of MCI due to AD vs non-AD MCI showed an AUC = 0.89 [0.85-0.93]. A cut-off value of 1.30 pg/ml of plasma pTau181 exhibited a sensitivity of 93.57% [88.72-96.52], specificity of 72.38% [62.51-79.01], VPP of 77.85% [70.61-83.54], and 8.30% false negatives in the subjects with MCI of the testing cohort. The HR of cox regression showed that patients with MCI up to this cut-off value exhibited a HR = 1.84 [1.05-3.22] higher risk to convert to AD dementia than patients with MCI below the cut-off value. Interpretation: Plasma pTau181 has the potential to be used in the memory clinics as a screening biomarker of AD pathology in subjects with MCI, presenting a valuable prognostic utility in predicting the MCI conversion to AD dementia. In the context of a real-world population, a confirmatory test employing gold-standard procedures is still advisable. Funding: This study has been mainly funded by Ace Alzheimer Center Barcelona, Instituto de Salud Carlos III (ISCIII), Biomedical Research Networking Centre in Neurodegenerative Diseases (CIBERNED), Spanish Ministry of Science and Innovation, Fundaci & oacute;n ADEY, Fundaci & oacute;n Echevarne and Gr & iacute;fols S.A. Copyright (c) 2024 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Filiaciones:
Cano, A:
Ace Alzheimer Ctr Barcelona, Res Ctr, Barcelona, Spain
Ace Alzheimer Ctr Barcelona, Memory Clin, Barcelona, Spain
Biomed Res Networking Ctr Neurodegenerat Dis CIBER, Madrid, Spain
Capdevila, M:
Ace Alzheimer Ctr Barcelona, Res Ctr, Barcelona, Spain
Ace Alzheimer Ctr Barcelona, Memory Clin, Barcelona, Spain
Univ Barcelona, Fac Pharm & Food Sci, Dept Pharmacol Toxicol & Therapeut Chem, Barcelona, Spain
Puerta, R:
Ace Alzheimer Ctr Barcelona, Res Ctr, Barcelona, Spain
Ace Alzheimer Ctr Barcelona, Memory Clin, Barcelona, Spain
Arranz, J:
Univ Autonoma Barcelona, Biomed Res Inst St Pau IIB St Pau, Hosp Santa Creu & St Pau, Dept Neurol,St Pau Memory Unit, Barcelona, Spain
Montrreal, L:
Ace Alzheimer Ctr Barcelona, Res Ctr, Barcelona, Spain
Ace Alzheimer Ctr Barcelona, Memory Clin, Barcelona, Spain
de Rojas, I:
Ace Alzheimer Ctr Barcelona, Res Ctr, Barcelona, Spain
Ace Alzheimer Ctr Barcelona, Memory Clin, Barcelona, Spain
Biomed Res Networking Ctr Neurodegenerat Dis CIBER, Madrid, Spain
García-González, P:
Ace Alzheimer Ctr Barcelona, Res Ctr, Barcelona, Spain
Ace Alzheimer Ctr Barcelona, Memory Clin, Barcelona, Spain
Biomed Res Networking Ctr Neurodegenerat Dis CIBER, Madrid, Spain
Olivé, C:
Ace Alzheimer Ctr Barcelona, Res Ctr, Barcelona, Spain
Ace Alzheimer Ctr Barcelona, Memory Clin, Barcelona, Spain
García-Gutiérrez, F:
Ace Alzheimer Ctr Barcelona, Res Ctr, Barcelona, Spain
Ace Alzheimer Ctr Barcelona, Memory Clin, Barcelona, Spain
Sotolongo-Grau, O:
Ace Alzheimer Ctr Barcelona, Res Ctr, Barcelona, Spain
Ace Alzheimer Ctr Barcelona, Memory Clin, Barcelona, Spain
Orellana, A:
Ace Alzheimer Ctr Barcelona, Res Ctr, Barcelona, Spain
Ace Alzheimer Ctr Barcelona, Memory Clin, Barcelona, Spain
Biomed Res Networking Ctr Neurodegenerat Dis CIBER, Madrid, Spain
Aguilera, N:
Ace Alzheimer Ctr Barcelona, Res Ctr, Barcelona, Spain
Ace Alzheimer Ctr Barcelona, Memory Clin, Barcelona, Spain
Ramis, M:
Ace Alzheimer Ctr Barcelona, Res Ctr, Barcelona, Spain
Ace Alzheimer Ctr Barcelona, Memory Clin, Barcelona, Spain
Rosende-Roca, M:
Ace Alzheimer Ctr Barcelona, Res Ctr, Barcelona, Spain
Ace Alzheimer Ctr Barcelona, Memory Clin, Barcelona, Spain
Biomed Res Networking Ctr Neurodegenerat Dis CIBER, Madrid, Spain
Lleó, A:
Biomed Res Networking Ctr Neurodegenerat Dis CIBER, Madrid, Spain
Univ Autonoma Barcelona, Biomed Res Inst St Pau IIB St Pau, Hosp Santa Creu & St Pau, Dept Neurol,St Pau Memory Unit, Barcelona, Spain
Fortea, J:
Biomed Res Networking Ctr Neurodegenerat Dis CIBER, Madrid, Spain
Univ Autonoma Barcelona, Biomed Res Inst St Pau IIB St Pau, Hosp Santa Creu & St Pau, Dept Neurol,St Pau Memory Unit, Barcelona, Spain
Fundacio Catalana Sindrome, Barcelona Med Ctr, Barcelona, Spain
Tartari, JP:
Ace Alzheimer Ctr Barcelona, Res Ctr, Barcelona, Spain
Ace Alzheimer Ctr Barcelona, Memory Clin, Barcelona, Spain
Lafuente, A:
Ace Alzheimer Ctr Barcelona, Res Ctr, Barcelona, Spain
Ace Alzheimer Ctr Barcelona, Memory Clin, Barcelona, Spain
Vargas, L:
Ace Alzheimer Ctr Barcelona, Res Ctr, Barcelona, Spain
Ace Alzheimer Ctr Barcelona, Memory Clin, Barcelona, Spain
Pérez-Cordón, A:
Ace Alzheimer Ctr Barcelona, Res Ctr, Barcelona, Spain
Ace Alzheimer Ctr Barcelona, Memory Clin, Barcelona, Spain
Muñoz, N:
Ace Alzheimer Ctr Barcelona, Res Ctr, Barcelona, Spain
Ace Alzheimer Ctr Barcelona, Memory Clin, Barcelona, Spain
Sanabria, A:
Ace Alzheimer Ctr Barcelona, Res Ctr, Barcelona, Spain
Ace Alzheimer Ctr Barcelona, Memory Clin, Barcelona, Spain
Alegret, M:
Ace Alzheimer Ctr Barcelona, Res Ctr, Barcelona, Spain
Ace Alzheimer Ctr Barcelona, Memory Clin, Barcelona, Spain
Biomed Res Networking Ctr Neurodegenerat Dis CIBER, Madrid, Spain
Morató, X:
Ace Alzheimer Ctr Barcelona, Res Ctr, Barcelona, Spain
Ace Alzheimer Ctr Barcelona, Memory Clin, Barcelona, Spain
Tárraga, L:
Ace Alzheimer Ctr Barcelona, Res Ctr, Barcelona, Spain
Ace Alzheimer Ctr Barcelona, Memory Clin, Barcelona, Spain
Biomed Res Networking Ctr Neurodegenerat Dis CIBER, Madrid, Spain
Fernández, V:
Ace Alzheimer Ctr Barcelona, Res Ctr, Barcelona, Spain
Ace Alzheimer Ctr Barcelona, Memory Clin, Barcelona, Spain
Marquié, M:
Ace Alzheimer Ctr Barcelona, Res Ctr, Barcelona, Spain
Ace Alzheimer Ctr Barcelona, Memory Clin, Barcelona, Spain
Biomed Res Networking Ctr Neurodegenerat Dis CIBER, Madrid, Spain
Valero, S:
Ace Alzheimer Ctr Barcelona, Res Ctr, Barcelona, Spain
Ace Alzheimer Ctr Barcelona, Memory Clin, Barcelona, Spain
Biomed Res Networking Ctr Neurodegenerat Dis CIBER, Madrid, Spain
Alcolea, D:
Biomed Res Networking Ctr Neurodegenerat Dis CIBER, Madrid, Spain
Univ Autonoma Barcelona, Biomed Res Inst St Pau IIB St Pau, Hosp Santa Creu & St Pau, Dept Neurol,St Pau Memory Unit, Barcelona, Spain
Boada, M:
Ace Alzheimer Ctr Barcelona, Res Ctr, Barcelona, Spain
Ace Alzheimer Ctr Barcelona, Memory Clin, Barcelona, Spain
Biomed Res Networking Ctr Neurodegenerat Dis CIBER, Madrid, Spain
Ruiz, A:
Ace Alzheimer Ctr Barcelona, Res Ctr, Barcelona, Spain
Ace Alzheimer Ctr Barcelona, Memory Clin, Barcelona, Spain
Biomed Res Networking Ctr Neurodegenerat Dis CIBER, Madrid, Spain
Univ Texas Hlth Sci Ctr San Antonio, Glenn Biggs Inst Alzheimers & Neurodegenerat Dis, San Antonio, TX USA
Green Accepted, gold
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