The Alzheimer’s Disease Diagnosis and Plasma Phospho-Tau217 (ADAPT) study stage 1: validating clinical cut-points against CSF and amyloid PET

  1. Ashvini Keshavan
  2. Katharine Wiltshire
  3. Ryan Wee
  4. Irene Gorostiaga Belio
  5. Katie Tucker
  6. Melanie Hart
  7. Michael P. Lunn
  8. Michael C. B. David
  9. Laura Rizzo
  10. Omid Sadeghi-Alavijeh
  11. Patricia Wilson
  12. Daniel P. Gale
  13. Amanda J. Heslegrave
  14. Henrik Zetterberg
  15. Nick C. Fox
  16. Paresh Malhotra
  17. Jonathan M. Schott
0 evaluations Published on
Read the full article Related papers
This article on Sciety

Abstract

INTRODUCTION

We validated plasma p-tau217 cut-points for Alzheimer’s disease (AD) diagnosis using two commercial assays in two biomarker-defined cohorts and examined influences of pre-analytical factors and chronic kidney disease (CKD) on p-tau217 concentrations.

METHODS

Lumipulse (Fujirebio) and ALZpath (Quanterix) assays quantified plasma p-tau217 in symptomatic patients (AD status definition CSF n=257; amyloid PET n=76). ROC analyses established ≥95% sensitivity/specificity cut-points. In separate cohorts we evaluated the impact of pre-analytical handling/transport variations (n=40/10) and cognitively normal (CN)-CKD individuals (n=58).

RESULTS

Diagnostic accuracy was similar (AUROC Lumipulse 0.947; ALZpath 0.940). Lumipulse p-tau217 achieved 95% sensitivity and 97% specificity using dual cut-points (0.153/0.422 pg/mL), producing indeterminate results in 19.4% (CSF-defined) and 34.2% (PET-defined). P-tau217 concentrations were stable across handling conditions and kit lots, and mostly in the low-to-intermediate range in CN-CKD.

DISCUSSION

Lumipulse plasma p-tau217, now available in our UKAS-accredited clinical NHS laboratory, will be used in a randomized trial of p-tau217 result disclosure in memory services.

Related articles

Related articles are currently not available for this article.