journal articles
EVALUATION OF PLASMA P-TAU217 BIOMARKERS IN DETECTING AMYLOID PATHOLOGY AND PREDICTING COGNITIVE OUTCOMES: OBSERVATIONS FROM JAPANESE ALZHEIMER’S DISEASE NEUROIMAGING INITIATIVE COHORT
Kensaku Kasuga, Masataka Kikuchi, Emiko Kikkawa-Saito, Tamao Tsukie, Takanobu Ishiguro, Akinori Miyashita, Takeshi Iwatsubo, the Japanese Alzheimer’s Disease Neuroimaging Initiative, Takeshi Ikeuchi
BACKGROUND AND OBJECTIVES: Plasma phosphorylated tau 217 (p-tau217) has shown strong potential as a blood-based biomarker for detecting amyloid pathology in Alzheimer’s disease. This study evaluated the diagnostic and prognostic utility of plasma biomarkers, including p-tau217, in participants from the Japanese Alzheimer’s Disease Neuroimaging Initiative (J-ADNI) cohort.
METHODS: We analyzed paired plasma and CSF samples from 172 J-ADNI participants. CSF and plasma biomarkers were quantified using the LUMIPULSE platform, and the same plasma samples were analyzed using the Simoa platform. The diagnostic accuracy for detecting amyloid pathology and the prognostic value of plasma p-tau217 biomarkers were assessed. Associations between plasma p-tau217 and polygenic risk scores (PRS), as well as potential confounding factors, were examined.
RESULTS: Plasma p-tau217 levels measured using Lumipulse and Simoa assays were highly correlated (p < 0.001). All plasma p-tau217 assays showed high diagnostic accuracy for CSF Aβ42/Aβ40-defined amyloid pathology (AUC = 0.98). A single cutoff point based on the Youden index for p-tau217 and p-tau217/Aβ42 achieved >90% specificity and >90% sensitivity. The predefined FDA-approved two-cutoff model for p-tau217/Aβ42 was applicable to this cohort. PRS was significantly associated with plasma p-tau217 independently of APOE genotypes. Subjects with higher plasma p-tau217 levels showed a significantly increased risk of conversion to dementia and larger longitudinal cognitive declines. Plasma p-tau217 levels were significantly influenced by the body mass index, estimated glomerular filtration rate, and high-density lipoprotein cholesterol.
CONCLUSIONS: Plasma p-tau217 and p-tau217/Aβ42 are robust biomarkers for AD diagnosis and prognosis in the Japanese population.
CITATION:
Kensaku Kasuga ; Masataka Kikuchi ; Emiko Kikkawa-Saito ; Tamao Tsukie ; Takanobu Ishiguro ; Akinori Miyashita ; Takeshi Iwatsubo ; the Japanese Alzheimer’s Disease Neuroimaging Initiative ; Takeshi Ikeuchi (2026): Evaluation of plasma p-tau217 biomarkers in detecting amyloid pathology and predicting cognitive outcomes: Observations from Japanese Alzheimer’s disease neuroimaging initiative cohort. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100502