One scale for every p-tau217 blood test
Can we use a unified calibrator to standardize plasma p-tau217/BD-p-tau217 measurements from different assays into one common scale from which meaningful thresholds can be obtained?
The problem
What's the challenge, and why is it so hard to solve?
Plasma p-tau217 is a highly reliable blood-based biomarker that reflects amyloid build-up in the brain. It is increasingly used for Alzheimer's disease diagnosis; two assays have been FDA-approved and several other assays are research-use-only (RUO). However, absolute p-tau217 concentrations vary substantially across assays and measurement platforms, limiting the direct comparability of results and complicating clinical interpretation.
Our approach
How are we tackling the challenge?
Our approach has two steps. First, we use a semi-synthetic p-tau217 (SS-pT217) reference material as a common calibrator across four p-tau217 assays: the FDA-approved Lumipulse-pT217V, the NULISA-qpcr BD-p-tau217, and the Simoa ALZpath and Janssen p-tau217 assays. Second, using an initial set of samples, we calculated a correction factor for each assay that converts its results onto one common scale.
We will evaluate our two-step standardization approach in large cohorts to determine whether a common threshold on the unified scale can achieve comparable clinical performance across assays. Building on this framework, we will establish a standardized amyloid positivity ruler that enables direct interpretation of p-tau217 values and estimation of the likelihood of amyloid pathology, regardless of the assay used.
Why it matters
What difference could this make for patients and society?
Standardizing plasma p-tau217 measurements would be extremely valuable in clinical practice because it allows comparing measurements from various assays to standard thresholds to make clinical decisions. This facilitates clinical interpretation of plasma p-tau217 test results for AD diagnosis, prognosis, treatment eligibility determination, and longitudinal tracking of individual patient measurements regardless of the assay that produced the measurement, given it has a validated SS-pT217 curve.
What's next
Once we've solved this, what do we want to explore next?
After validating this approach in larger cohorts, we will develop a web application that standardizes p-tau217 measurements across assays and provides individualized estimates of amyloid pathology risk based on the unified scale. Clinicians could then use it to interpret an individual patient's results in the clinic.
Key publications
Where can I read more?
Team
Who's working on this?