Independent validation of the PrecivityAD2

Objective: The diagnostic performance of the Amyloid Probability Score 2 (APS2) - the algorithmic result of the PrecivityAD2 Methods: Plasma biomarker ratios Aβ42/40 and p-tau217/np-tau217 (expressed as %p-tau217) were quantified and incorporated into the APS2 algorithm in samples obtained from 192 Alzheimer's Disease Neuroimaging Initiative participants with CI (70% mild cognitive impairment / 30% dementia). APS2 diagnostic performance was determined using amyloid positron emission tomography (PET) as the reference standard. Plasma biomarkers were quantified in a CLIA-certified, CAP-accredited laboratory (C2N Diagnostics, St. Louis, MO) using liquid chromatography-tandem mass spectrometry. Results: APS2 values were significantly higher in the 56% of CI participants with a positive amyloid PET scan. Concordance with amyloid PET was high (AUC-ROC 0.95 (95%CI): 0.93-0.98); 54% of participants had a positive APS2. The previously validated APS2 cut point yielded an overall accuracy of 91% (95%CI: 86-94%), sensitivity 90% (95%CI: 83-94%) and specificity 92% (95%CI: 84-96%). Interpretation: The PrecivityAD2 blood test's APS2 identified brain amyloid pathology with accuracy, sensitivity, and specificity ≥ 90% in this intended use population. This external validation reaffirms the diagnostic robustness of this blood biomarker test and supports its use as a confirmatory test, consistent with published expert recommendations, for assessment of presence or absence of brain amyloid pathology in symptomatic patients.