Performance of plasma pTau217, pTau181 and their ratios to Aβ42 in detecting Aβ pathology using a China-developed direct chemiluminescence assay

BACKGROUND: Increasing evidence indicates that blood-based biomarkers, particularly phosphorylated tau (pTau) 217 and the pTau217/amyloid‑β (Aβ) 42 ratio, demonstrate strong diagnostic performance for Alzheimer's disease (AD) and may offer a minimally invasive alternative to cerebrospinal fluid (CSF) assays and Aβ PET imaging. There is an urgent need to develop local plasma pTau217 and pTau217/Aβ42 ratio assay and to establish population-appropriate diagnostic cutoffs tailored to Chinese populations. METHODS: This study included 831 individuals from a community-based memory screening cohort and 301 patients from a hospital-based cohort with confirmed Aβ pathology. Plasma pTau217, pTau181, and their ratios to Aβ42 were measured using a high-sensitivity direct chemiluminescence (DCL) immunoassay incorporating proprietary China-developed antibodies. Data-driven Gaussian mixture modeling (GMM) was applied to the community cohort to derive biomarker cutoffs; the diagnostic performance of these cutoffs was validated in the patients with confirmed Aβ pathology. A two-cutoff approach was established in the hospital-based cohort. Multivariate regression analysis was performed to assessed potential confounding effects from routine blood biochemical parameters. RESULTS: GMM identified cutoffs of 4.380 pg/mL for pTau217 and 0.670 for the pTau217/Aβ42 ratio. These values closely matched cutoffs derived from the maximum Youden index (4.296 pg/mL for pTau217 and 0.706 for pTau217/Aβ42) and achieved high diagnostic accuracy (up to 89%) for Aβ pathology in the hospital-based cohort with confirmed Aβ pathology, outperforming pTau181-based measures. Only the pTau217/Aβ42 ratio was unaffected by routine plasma biochemistry. Using a two-cutoff workflow, pTau217 or the pTau217/Aβ42 ratio definitively classified approximately 90% of patients as positive or negative, leaving an intermediate-risk zone of < 10%. CONCLUSIONS: The China-developed DCL immunoassay reliably measures plasma pTau217 and the pTau217/Aβ42 ratio with high diagnostic accuracy for detecting Aβ pathology. The biochemical stability of the pTau217/Aβ42 ratio supports its potential as a practical, less invasive alternative to CSF or PET testing in Chinese populations.