Clinical performance and head-to-head comparison of CSF p-tau235 with p-tau181, p-tau217 and p-tau231 in two memory clinic cohorts - Université Paris Cité Accéder directement au contenu
Article Dans Une Revue Alzheimer's Research and Therapy Année : 2023

Clinical performance and head-to-head comparison of CSF p-tau235 with p-tau181, p-tau217 and p-tau231 in two memory clinic cohorts

Juan Lantero-Rodriguez
  • Fonction : Auteur
Aida Fernández-Lebrero
  • Fonction : Auteur
Paula Ortiz-Romero
  • Fonction : Auteur
Anniina Snellman
  • Fonction : Auteur
Laia Montoliu-Gaya
  • Fonction : Auteur
Wagner S Brum
  • Fonction : Auteur
Julien Dumurgier
  • Fonction : Auteur
Albert Puig-Pijoan
  • Fonction : Auteur
Irene Navalpotro-Gómez
  • Fonction : Auteur
Greta García-Escobar
  • Fonction : Auteur
Thomas K Karikari
  • Fonction : Auteur
Eugeen Vanmechelen
  • Fonction : Auteur
Nicholas J Ashton
  • Fonction : Auteur
Henrik Zetterberg
  • Fonction : Auteur
Marc Suárez-Calvet
  • Fonction : Auteur
Kaj Blennow
  • Fonction : Auteur

Résumé

Background 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. Methods 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 1–42/40 ratio, p-tau181 and t-tau] and in-house developed Simoa CSF p-tau181, p-tau217 and p-tau231). Results 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. Conclusions 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.
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hal-04086958 , version 1 (02-05-2023)

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Juan Lantero-Rodriguez, Agathe Vrillon, Aida Fernández-Lebrero, Paula Ortiz-Romero, Anniina Snellman, et al.. Clinical performance and head-to-head comparison of CSF p-tau235 with p-tau181, p-tau217 and p-tau231 in two memory clinic cohorts. Alzheimer's Research and Therapy, 2023, 15 (1), pp.48. ⟨10.1186/s13195-023-01201-0⟩. ⟨hal-04086958⟩

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