The Taiwan‐ADNI workflow toward integrating plasma p‐tau217 into prediction models for the risk of Alzheimer's disease and tau burden

Abstract

INTRODUCTIONWe integrated plasma biomarkers from the Taiwan Alzheimer's Disease Neuroimaging Initiative and propose a workflow to identify individuals showing amyloid‐positive positron emission tomography (PET) with low/intermediate tau burden based on [18F]Florzolotau PET‐based quantification.METHODSWe assessed 361 participants across the Alzheimer's disease (AD) and non‐AD continuum and measured plasma phosphorylated tau (p‐tau)217, p‐tau181, amyloid beta (Aβ)42/40 ratio, neurofilament light chain, and glial fibrillary acidic protein levels at two medical centers. We evaluated the diagnostic potential of these biomarkers.RESULTSAmong all plasma biomarkers, p‐tau217 had the highest consistency with amyloid PET results (area under the curve = 0.94), and a cutoff value could have reduced the number of confirmatory amyloid PET scans by 57.5%. In amyloid PET–positive cases intending to use anti‐amyloid therapy, p‐tau217 level, along with clinical parameters, had the highest predictive ability for low/intermediate tau burden.DISCUSSIONA two‐step workflow based on p‐tau217 and confirmatory amyloid PET could accurately classify AD patients showing low/intermediate tau burden.Highlights The emergence of anti‐amyloid therapy increases the need to accurately diagnose Alzheimer's disease (AD). The use of plasma biomarkers, especially phosphorylated tau 217 (p‐tau217), can help in the diagnosis of AD. P‐tau217 is a better predictor of amyloid positron emission tomography (PET) positivity than other core biomarkers. In amyloid PET–positive individuals, p‐tau217 can predict tau burden. We propose a two‐step workflow to identify AD cases suitable for treatment.