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A novel ultrasensitive assay for plasma p-tau217: Performance in individuals with subjective cognitive decline and early Alzheimer's disease

Gonzalez-Ortiz F, Ferreira PCL, González-Escalante A, Montoliu-Gaya L, Ortiz-Romero P, Kac PR, Turton M, Kvartsberg H, Ashton NJ, Zetterberg H, Harrison P, Bellaver B, Povala G, Villemagne VL, Pascoal TA, Ganguli M, Cohen AD, Minguillon C, Contador J, Suárez-Calvet M, Karikari TK, Blennow K

Resum

Introduction: Detection of Alzheimer's disease (AD) pathophysiology among individuals with mild cognitive changes and those experiencing subjective cognitive decline (SCD) remains challenging. Plasma phosphorylated tau 217 (p-tau217) is one of the most promising of the emerging biomarkers for AD. However, accessible methods are limited.

Methods: We employed a novel p-tau217 immunoassay (University of Gothenburg [UGOT] p-tau217) in four independent cohorts (n = 308) including a cerebrospinal fluid (CSF) biomarker-classified cohort (Discovery), two cohorts consisting mostly of cognitively unimpaired (CU) and mild cognitively impaired (MCI) participants (MYHAT and Pittsburgh), and a population-based cohort of individuals with SCD (Barcelonaβeta Brain Research Center's Alzheimer's At-Risk Cohort [β-AARC]).

Results: UGOT p-tau217 showed high accuracy (area under the curve [AUC] = 0.80-0.91) identifying amyloid beta (Aβ) pathology, determined either by Aβ positron emission tomography or CSF Aβ42/40 ratio. In individuals experiencing SCD, UGOT p-tau217 showed high accuracy identifying those with a positive CSF Aβ42/40 ratio (AUC = 0.91).

Discussion: UGOT p-tau217 can be an easily accessible and efficient way to screen and monitor patients with suspected AD pathophysiology, even in the early stages of the continuum.

Keywords: Alzheimer's disease; blood biomarkers; early diagnosis; p-tau217; preclinical; subjective cognitive decline.

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Referència

Gonzalez-Ortiz F, Ferreira PCL, González-Escalante A, Montoliu-Gaya L, Ortiz-Romero P, Kac PR, Turton M, Kvartsberg H, Ashton NJ, Zetterberg H, Harrison P, Bellaver B, Povala G, Villemagne VL, Pascoal TA, Ganguli M, Cohen AD, Minguillon C, Contador J, Suárez-Calvet M, Karikari TK, Blennow K. A novel ultrasensitive assay for plasma p-tau217: Performance in individuals with subjective cognitive decline and early Alzheimer's disease. Alzheimers Dement. 2023 Nov 17. doi: 10.1002/alz.13525. Epub ahead of print. PMID: 37975513.