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

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.

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.

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.

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.

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.