Clinical performance and head-to-head comparison of CSF p-tau235 with p-tau181, p-tau217 and p-tau231 in two memory clinic cohorts
Lantero-Rodríguez, Juan (University of Gothenburg)
Vrillon, Agathe (Groupe Hospitalo Universitaire Assistance Publique Hôpitaux de Paris Nord Hôpital Lariboisière Fernand-Widal)
Fernández-Lebrero, Aida (Institut Hospital del Mar d'Investigacions Mèdiques)
Ortiz-Romero, Paula (Institut Hospital del Mar d'Investigacions Mèdiques)
Snellman, Anniina (University of Turku)
Montoliu-Gaya, Laia (the Sahlgrenska Academy at the University of Gothenburg)
Brum, Wagner S. (Universidade Federal do Rio Grande do Sul)
Cognat, Emmanuel (Groupe Hospitalo Universitaire Assistance Publique Hôpitaux de Paris Nord Hôpital Lariboisière Fernand-Widal)
Dumurgier, Julien (Groupe Hospitalo Universitaire Assistance Publique Hôpitaux de Paris Nord Hôpital Lariboisière Fernand-Widal)
Puig-Pijoan, Albert (Universitat Autònoma de Barcelona. Departament de Medicina)
Navalpotro-Gómez, Irene (Institut Hospital del Mar d'Investigacions Mèdiques)
García-Escobar, Greta (Institut Hospital del Mar d'Investigacions Mèdiques)
Karikari, Thomas K. (University of Pittsburgh)
Vanmechelen, Eugeen (ADx NeuroSciences (Ghent, Bèlgica))
Ashton, Nicholas J. (NIHR Biomedical Research Centre for Mental Health (Londres, Regne Unit))
Zetterberg, Henrik (University of Wisconsin School of Medicine and Public Health)
Suárez-Calvet, Marc (Institut Hospital del Mar d'Investigacions Mèdiques)
Paquet, Claire (Groupe Hospitalo Universitaire Assistance Publique Hôpitaux de Paris Nord Hôpital Lariboisière Fernand-Widal)
Blennow, Kaj (Sahlgrenska University Hospital (Suècia))

Data:	2023
Resum:	Cerebrospinal fluid (CSF) p-tau235 is a novel biomarker highly specific of Alzheimer's disease (AD). However, CSF p-tau235 has only been studied in well-characterized research cohorts, which do not fully reflect the patient landscape found in clinical settings. Therefore, in this multicentre study, we investigated the performance of CSF p-tau235 to detect symptomatic AD in clinical settings and compared it with CSF p-tau181, p-tau217 and p-tau231. CSF p-tau235 was measured using an in-house single molecule array (Simoa) assay in two independent memory clinic cohorts: Paris cohort (Lariboisière Fernand-Widal University Hospital Paris, France; n =212) and BIODEGMAR cohort (Hospital del Mar, Barcelona, Spain; n =175). Patients were classified by the syndromic diagnosis (cognitively unimpaired [CU], mild cognitive impairment [MCI] or dementia) and their biological diagnosis (amyloid-beta [Aβ]+ or Aβ ). Both cohorts included detailed cognitive assessments and CSF biomarker measurements (clinically validated core AD biomarkers [Lumipulse CSF Aβ ratio, p-tau181 and t-tau] and in-house developed Simoa CSF p-tau181, p-tau217 and p-tau231). High CSF p-tau235 levels were strongly associated with CSF amyloidosis regardless of the clinical diagnosis, being significantly increased in MCI Aβ+ and dementia Aβ+ when compared with all other Aβ- groups (Paris cohort: P ˂0. 0001 for all; BIODEGMAR cohort: P ˂0. 05 for all). CSF p-tau235 was pronouncedly increased in the A+T+ profile group compared with A-T- and A+T- groups (P ˂0. 0001 for all). Moreover, CSF p-tau235 demonstrated high diagnostic accuracies identifying CSF amyloidosis in symptomatic cases (AUCs=0. 86 to 0. 96) and discriminating AT groups (AUCs=0. 79 to 0. 98). Overall, CSF p-tau235 showed similar performances to CSF p-tau181 and CSF p-tau231 when discriminating CSF amyloidosis in various scenarios, but lower than CSF p-tau217. Finally, CSF p-tau235 associated with global cognition and memory domain in both cohorts. CSF p-tau235 was increased with the presence of CSF amyloidosis in two independent memory clinic cohorts. CSF p-tau235 accurately identified AD in both MCI and dementia patients. Overall, the diagnostic performance of CSF p-tau235 was comparable to that of other CSF p-tau measurements, indicating its suitability to support a biomarker-based AD diagnosis in clinical settings. The online version contains supplementary material available at 10. 1186/s13195-023-01201-0.
Ajuts:	Instituto de Salud Carlos III PI19/00155
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Alzheimer's disease ; CSF ; Biomarkers ; P-tau235 ; P-tau181 ; P-tau217 ; P-tau231 ; Memory clinic
Publicat a:	Alzheimer's research & therapy, Vol. 15 (march 2023) , ISSN 1758-9193

DOI: 10.1186/s13195-023-01201-0
PMID: 36899441

15 p, 2.2 MB

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