Clinical value of plasma pTau181 to predict Alzheimer's disease pathology in a large real-world cohort of a memory clinicResearch in context
Amanda Cano,
María Capdevila,
Raquel Puerta,
Javier Arranz,
Laura Montrreal,
Itziar de Rojas,
Pablo García-González,
Claudia Olivé,
Fernando García-Gutiérrez,
Oscar Sotolongo-Grau,
Adelina Orellana,
Nuria Aguilera,
Maribel Ramis,
Maitee Rosende-Roca,
Alberto Lleó,
Juan Fortea,
Juan Pablo Tartari,
Asunción Lafuente,
Liliana Vargas,
Alba Pérez-Cordón,
Nathalia Muñoz,
Ángela Sanabria,
Montserrat Alegret,
Xavier Morató,
Lluís Tárraga,
Victoria Fernández,
Marta Marquié,
Sergi Valero,
Daniel Alcolea,
Mercè Boada,
Agustín Ruiz
Affiliations
Amanda Cano
Research Center and Memory Clinic, Ace Alzheimer Center Barcelona, Barcelona, Spain; Biomedical Research Networking Centre in Neurodegenerative Diseases (CIBERNED), Madrid, Spain; Corresponding author. Head of the Molecular Biology and Biomarkers Program, Ace Alzheimer Center Barcelona, C/ Marquès de Sentmenat, 57, 08029, Barcelona, Spain.
María Capdevila
Research Center and Memory Clinic, Ace Alzheimer Center Barcelona, Barcelona, Spain; Department of Pharmacology, Toxicology and Therapeutic Chemistry, Faculty of Pharmacy and Food Science, Universitat de Barcelona, Spain
Raquel Puerta
Research Center and Memory Clinic, Ace Alzheimer Center Barcelona, Barcelona, Spain
Javier Arranz
Sant Pau Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB Sant Pau), Universitat Autònoma de Barcelona, Barcelona, Spain
Laura Montrreal
Research Center and Memory Clinic, Ace Alzheimer Center Barcelona, Barcelona, Spain
Itziar de Rojas
Research Center and Memory Clinic, Ace Alzheimer Center Barcelona, Barcelona, Spain; Biomedical Research Networking Centre in Neurodegenerative Diseases (CIBERNED), Madrid, Spain
Pablo García-González
Research Center and Memory Clinic, Ace Alzheimer Center Barcelona, Barcelona, Spain; Biomedical Research Networking Centre in Neurodegenerative Diseases (CIBERNED), Madrid, Spain
Claudia Olivé
Research Center and Memory Clinic, Ace Alzheimer Center Barcelona, Barcelona, Spain
Fernando García-Gutiérrez
Research Center and Memory Clinic, Ace Alzheimer Center Barcelona, Barcelona, Spain
Oscar Sotolongo-Grau
Research Center and Memory Clinic, Ace Alzheimer Center Barcelona, Barcelona, Spain
Adelina Orellana
Research Center and Memory Clinic, Ace Alzheimer Center Barcelona, Barcelona, Spain; Biomedical Research Networking Centre in Neurodegenerative Diseases (CIBERNED), Madrid, Spain
Nuria Aguilera
Research Center and Memory Clinic, Ace Alzheimer Center Barcelona, Barcelona, Spain
Maribel Ramis
Research Center and Memory Clinic, Ace Alzheimer Center Barcelona, Barcelona, Spain
Maitee Rosende-Roca
Research Center and Memory Clinic, Ace Alzheimer Center Barcelona, Barcelona, Spain; Biomedical Research Networking Centre in Neurodegenerative Diseases (CIBERNED), Madrid, Spain
Alberto Lleó
Biomedical Research Networking Centre in Neurodegenerative Diseases (CIBERNED), Madrid, Spain; Sant Pau Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB Sant Pau), Universitat Autònoma de Barcelona, Barcelona, Spain
Juan Fortea
Biomedical Research Networking Centre in Neurodegenerative Diseases (CIBERNED), Madrid, Spain; Sant Pau Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB Sant Pau), Universitat Autònoma de Barcelona, Barcelona, Spain; Barcelona Down Medical Center, Fundació Catalana Síndrome de Down, Barcelona, Spain
Juan Pablo Tartari
Research Center and Memory Clinic, Ace Alzheimer Center Barcelona, Barcelona, Spain
Asunción Lafuente
Research Center and Memory Clinic, Ace Alzheimer Center Barcelona, Barcelona, Spain
Liliana Vargas
Research Center and Memory Clinic, Ace Alzheimer Center Barcelona, Barcelona, Spain
Alba Pérez-Cordón
Research Center and Memory Clinic, Ace Alzheimer Center Barcelona, Barcelona, Spain
Nathalia Muñoz
Research Center and Memory Clinic, Ace Alzheimer Center Barcelona, Barcelona, Spain
Ángela Sanabria
Research Center and Memory Clinic, Ace Alzheimer Center Barcelona, Barcelona, Spain
Montserrat Alegret
Research Center and Memory Clinic, Ace Alzheimer Center Barcelona, Barcelona, Spain; Biomedical Research Networking Centre in Neurodegenerative Diseases (CIBERNED), Madrid, Spain
Xavier Morató
Research Center and Memory Clinic, Ace Alzheimer Center Barcelona, Barcelona, Spain
Lluís Tárraga
Research Center and Memory Clinic, Ace Alzheimer Center Barcelona, Barcelona, Spain; Biomedical Research Networking Centre in Neurodegenerative Diseases (CIBERNED), Madrid, Spain
Victoria Fernández
Research Center and Memory Clinic, Ace Alzheimer Center Barcelona, Barcelona, Spain
Marta Marquié
Research Center and Memory Clinic, Ace Alzheimer Center Barcelona, Barcelona, Spain; Biomedical Research Networking Centre in Neurodegenerative Diseases (CIBERNED), Madrid, Spain
Sergi Valero
Research Center and Memory Clinic, Ace Alzheimer Center Barcelona, Barcelona, Spain; Biomedical Research Networking Centre in Neurodegenerative Diseases (CIBERNED), Madrid, Spain
Daniel Alcolea
Biomedical Research Networking Centre in Neurodegenerative Diseases (CIBERNED), Madrid, Spain; Sant Pau Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB Sant Pau), Universitat Autònoma de Barcelona, Barcelona, Spain
Mercè Boada
Research Center and Memory Clinic, Ace Alzheimer Center Barcelona, Barcelona, Spain; Biomedical Research Networking Centre in Neurodegenerative Diseases (CIBERNED), Madrid, Spain
Agustín Ruiz
Research Center and Memory Clinic, Ace Alzheimer Center Barcelona, Barcelona, Spain; Biomedical Research Networking Centre in Neurodegenerative Diseases (CIBERNED), Madrid, Spain; Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, University of Texas Health Science Center, San Antonio, TX, USA
Summary: 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 Aβ(+) vs Aβ(−) 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, Fundación ADEY, Fundación Echevarne and Grífols S.A.