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

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.