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

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 mu...

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Authors: Lantero-Rodriguez, J., Vrillon, A., Fernández Lebrero, Aída, Ortiz-Romero, P., Snellman, A., Montoliu-Gaya, L., Brum, W.S., Cognat, E., Dumurgier, J., Puig-Pijoan, A., Navalpotro-Gómez, I., García-Escobar, G., Karikari, T.K., Vanmechelen, E., Ashton, N.J., Zetterberg, H., Suárez-Calvet, M., Paquet, C., Blennow, K.
Format: article
Publication Date:2023
Country:España
Institution:Servizo Galego de Saúde (SERGAS)
Repository:RUNA. Repositorio da Consellería de Sanidade e Sergas
OAI Identifier:oai:runa.sergas.gal:20.500.11940/21252
Online Access:https://portalcientifico.sergas.gal//documentos/642b36b4a1c8a315fd231c83
http://hdl.handle.net/20.500.11940/21252
Access Level:Open access
Keyword:Humans
Alzheimer Disease
Amyloid beta-Peptides
Amyloidosis
Biomarkers
Cognitive Dysfunction
tau Proteins
AS Santiago
CHUS
Description
Summary: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 [A?]+ or A? -). Both cohorts included detailed cognitive assessments and CSF biomarker measurements (clinically validated core AD biomarkers [Lumipulse CSF A?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 A?+ and dementia A?+ when compared with all other A?? 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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