Interchangeability of blood‐based biomarkers and PET to identify Alzheimer's disease pathology

Abstract INTRODUCTION Establishing interchangeability between blood biomarkers and amyloid‐positron emission tomography (PET) could help identify patients who would benefit from novel amyloid‐targeting therapies for Alzheimer's disease. METHODS Adult participants from the Global Alzheimer's Platform Foundation's Bio‐Hermes study with clinical diagnosis of mild cognitive impairment/mild dementia and available amyloid‐PET evaluations and Aβ42/40‐based PrecivityAD ® (by C2N Diagnostics) and/or phosphorylated tau at threonine 217 (p‐Tau217 (research use Meso Scale Discovery, Lilly) were included. Interchangeability between plasma‐based tests (per pre‐established thresholds) and amyloid‐PET stratifications was evaluated. RESULTS PrecivityAD ( N = 537) and p‐Tau217 ( N = 531) plasma‐based tests had high agreement with florbetapir‐PET (overall percent agreement: 80.7% and 90.1%, respectively) and accurately selected patients identified as florbetapir‐PET‐positive (positive predictive value: 86.0% and 88.0%, respectively). Further, they were non‐inferior to quantitative florbetapir‐PET (at 37 Centiloids) for identifying positive florbetapir‐PET visual reads. DISCUSSION Results support the hypothesis that blood biomarkers may be interchangeable with amyloid‐PET criteria for selecting patients who may benefit from treatment with novel amyloid‐targeting therapies. Highlights Interchangeability of plasma‐based tests and amyloid‐PET stratifications was demonstrated. Non‐inferiority of plasma‐based biomarkers to amyloid‐PET for identifying patients with AD pathology was observed. High agreement between plasma‐based test stratification and florbetapir‐PET expert visual read was observed.