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

Introduction: We 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.

Methods: We 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.

Results: Among 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.

Discussion: A 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.