VeraBIND Tau test, a novel plasma assay for active tau pathology, identifies individuals with positive tau‐PET signal, regardless of amyloid status

TL;DR

A new blood test called VeraBIND Tau can detect active tau pathology in people with or without amyloid buildup, offering a more accurate way to identify tau-related brain changes.

Contribution

The VeraBIND Tau test is a novel plasma assay that detects active tau pathology independently of amyloid status, improving the identification of tau aggregation.

Findings

VeraBIND Tau achieved 93% sensitivity and 95% specificity in detecting tau pathology using tau-PET as a reference.

The VeraBIND test outperformed pTau217 in identifying tau positivity in cases without amyloid, including some with low tau-PET signals.

VeraBIND Tau is more sensitive to early tau aggregation and can detect discordant A/T PET status in plasma.

Abstract

Plasma assays targeting tau phospho‐epitopes (e.g., pTau217) are frequently observed in the context of isolated amyloid‐β pathology (A+). Developing plasma assays associated with tau aggregation (T+) is an unmet challenge. Here, we present results of the VeraBIND Tau test, a plasma assay measuring how hyperphosphorylated tau (HPT) observed in a sample binds to normal tau, i.e., testing whether tau is pathologically active.

VeraBIND Tau is an in vitro bead‐based ELISA that uses chemiluminescence (Figure 1: overview). One hundred thirty‐three participants were recruited from an ongoing study at UCLouvain, Belgium, including 93 clinically normal (CN, 32A+) and 40 clinically impaired (MCI/AD, 36A+). A+ status was determined using either CSF (Aβ42≤544pg/mL) or amyloid‐PET (Centiloid≥20). F18MK6240 Tau‐PET status was determined visually as negative (Braak 0) or positive (Braak≥1). Plasma pTau217 was quantified using Lumipulse (Fujirebio).

The VeraBIND Tau plasma assay was weakly correlated with pTau217 concentration (R2=0.065, p = 0.02, Figure 2). Using tau‐PET as ground truth for tau, VeraBIND Tau detected 52 of 56 A+T+ participants (sensitivity=93%), and excluded tauopathy in 54 of 57 A‐T‐ participants (specificity=95%). With the same specificity (threshold=0.193pg/mL), pTau217 achieved similar sensitivity in A+T+ (51 of 56, 91%). However, nine of twelve A+T‐ participants had positive pTau217 whereas only four had positive VeraBIND test. In contrast, six of eight A‐T+ participants had negative pTau217, but positive VeraBIND test, including one FTLD and two probable PART cases. Except the FTLD case, the A‐T+ participants had relatively low tau‐PET signal (Braak 2‐3) and the only A‐ Braak=1 case was borderline (RLU=0.974, normal<1.0). The overall diagnostic accuracy of pTau217 was 90% for A‐/A+ and 82% for T‐/T+ while the accuracy of VeraBIND was 84% for A‐/A+ and 90% for T‐/T+.

Whereas pTau217 is more closely associated with amyloid than with tau‐PET results, VeraBIND Tau is highly sensitive to (early) tau‐PET positivity, indicating active tau aggregation, with or without amyloidosis. The mismatch between pTau217 and VeraBIND results provides a plasma indication of discordant A/T PET‐status.

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