Study Urges Global Adoption of p-Tau217 Blood Test for Early Alzheimer’s Detection

Phosphorylated tau (p-tau) has emerged as a promising blood biomarker for Alzheimer’s disease (AD) pathology, particularly p-tau217. Despite its high accuracy, limited availability of p-tau217 tests hinders broader research and clinical implementation of AD blood tests.

This study aims to assess the utility of a newly developed commercial immunoassay for plasma p-tau217 in detecting AD pathology and establish reference ranges for abnormal amyloid β (Aβ) across three distinct cohorts. 

The cohort study analyzed data from three single-center observational cohorts: Translational Biomarkers in Aging and Dementia (TRIAD), Wisconsin Registry for Alzheimer’s Prevention (WRAP), and Sant Pau Initiative on Neurodegeneration (SPIN). The study period ranged from October 2017 to August 2021 for TRIAD, February 2007 to November 2020 for WRAP, and March 2009 to November 2021 for SPIN.

Participants, both cognitively impaired and unimpaired, were categorized by Aβ and tau (AT) status using positron emission tomography (PET) or cerebrospinal fluid (CSF) biomarkers. Magnetic resonance imaging, Aβ PET, tau PET, CSF biomarkers, and the plasma p-tau217 assay were used as exposures. 

The study included 786 participants with a mean age of 66.3 years. The plasma p-tau217 assay demonstrated high accuracy in identifying elevated Aβ (AUC, 0.92-0.96) and tau pathology (AUC, 0.93-0.97) across all cohorts. These accuracies were comparable to CSF biomarkers for determining abnormal PET signals. A three-range reference for abnormal Aβ pathology showed reproducible results, reducing the need for confirmatory testing by approximately 80%. Longitudinally, plasma p-tau217 values exhibited an annual increase only in Aβ-positive individuals, with the highest increase observed in those with tau positivity. 

The study underscores the efficacy of a commercially available plasma p-tau217 immunoassay in accurately identifying biological AD, aligning with results obtained from CSF biomarkers. The consistency of cut-offs across cohorts suggests robustness in the assay’s performance. The assay not only detected longitudinal changes but also demonstrated sensitivity at the preclinical stage of AD. 

In conclusion, this research contributes valuable insights into the potential of a commercially available plasma p-tau217 immunoassay as a reliable tool for AD detection and monitoring. The assay’s accuracy in identifying abnormal Aβ and tau pathology, along with its reproducibility across diverse cohorts, supports its utility in research and clinical settings. The reduced need for confirmatory testing in Aβ pathology detection adds practical value. Furthermore, the ability to capture longitudinal changes, even in preclinical stages, positions this assay as a valuable tool for advancing AD research and diagnosis. 

The findings advocate for the wider adoption of plasma p-tau217 as a specific and accessible blood biomarker for AD pathology. Its comparable performance to CSF biomarkers, along with its longitudinal tracking capabilities, suggests that it could play a pivotal role in advancing the development and implementation of blood-based AD tests, ultimately contributing to earlier and more accurate diagnosis of Alzheimer’s disease. 

Journal Reference  

Ashton NJ, Brum WS, Di Molfetta G, et al. Diagnostic Accuracy of a Plasma Phosphorylated Tau 217 Immunoassay for Alzheimer Disease Pathology. JAMA Neurol. Published online January 22, 2024. doi:10.1001/jamaneurol.2023.5319.