Clinical validation of the PrecivityAD2 blood test: A mass spectrometry-based test with algorithm combining %p-tau217 and Aβ42/40 ratio to identify presence of brain amyloid

Alzheimers Dement. 2024 May;20(5):3179-3192. doi: 10.1002/alz.13764. Epub 2024 Mar 16.

Abstract

Background: With the availability of disease-modifying therapies for Alzheimer's disease (AD), it is important for clinicians to have tests to aid in AD diagnosis, especially when the presence of amyloid pathology is a criterion for receiving treatment.

Methods: High-throughput, mass spectrometry-based assays were used to measure %p-tau217 and amyloid beta (Aβ)42/40 ratio in blood samples from 583 individuals with suspected AD (53% positron emission tomography [PET] positive by Centiloid > 25). An algorithm (PrecivityAD2 test) was developed using these plasma biomarkers to identify brain amyloidosis by PET.

Results: The area under the receiver operating characteristic curve (AUC-ROC) for %p-tau217 (0.94) was statistically significantly higher than that for p-tau217 concentration (0.91). The AUC-ROC for the PrecivityAD2 test output, the Amyloid Probability Score 2, was 0.94, yielding 88% agreement with amyloid PET. Diagnostic performance of the APS2 was similar by ethnicity, sex, age, and apoE4 status.

Discussion: The PrecivityAD2 blood test showed strong clinical validity, with excellent agreement with brain amyloidosis by PET.

Keywords: Alzheimer's; amyloid beta; blood biomarker; clinical validity; diagnostic; p‐tau217.

Publication types

  • Validation Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Algorithms*
  • Alzheimer Disease* / blood
  • Alzheimer Disease* / diagnosis
  • Alzheimer Disease* / diagnostic imaging
  • Amyloid beta-Peptides* / blood
  • Biomarkers* / blood
  • Brain* / diagnostic imaging
  • Brain* / metabolism
  • Female
  • Humans
  • Male
  • Mass Spectrometry*
  • Middle Aged
  • Peptide Fragments* / blood
  • Positron-Emission Tomography*
  • ROC Curve
  • tau Proteins* / blood