Title |
Clinical performance and head-to-head comparison of CSF p-tau235 with p-tau181, p-tau217 and p-tau231 in two memory clinic cohorts
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Published in |
Alzheimer's Research & Therapy, March 2023
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DOI | 10.1186/s13195-023-01201-0 |
Pubmed ID | |
Authors |
Juan Lantero-Rodriguez, Agathe Vrillon, Aida Fernández-Lebrero, Paula Ortiz-Romero, Anniina Snellman, Laia Montoliu-Gaya, Wagner S. Brum, Emmanuel Cognat, Julien Dumurgier, Albert Puig-Pijoan, Irene Navalpotro-Gómez, Greta García-Escobar, Thomas K. Karikari, Eugeen Vanmechelen, Nicholas J. Ashton, Henrik Zetterberg, Marc Suárez-Calvet, Claire Paquet, Kaj Blennow |
Abstract |
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 Aβ1-42/40 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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
Spain | 3 | 33% |
Sweden | 1 | 11% |
France | 1 | 11% |
United Kingdom | 1 | 11% |
Unknown | 3 | 33% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 6 | 67% |
Scientists | 3 | 33% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 16 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 4 | 25% |
Student > Doctoral Student | 2 | 13% |
Other | 1 | 6% |
Student > Bachelor | 1 | 6% |
Lecturer | 1 | 6% |
Other | 2 | 13% |
Unknown | 5 | 31% |
Readers by discipline | Count | As % |
---|---|---|
Neuroscience | 5 | 31% |
Chemical Engineering | 1 | 6% |
Biochemistry, Genetics and Molecular Biology | 1 | 6% |
Engineering | 1 | 6% |
Unknown | 8 | 50% |