Xinyi Lv, Kaiyuan Shen, Qianhua Zhao, Guoping Peng, Huayan Liu, Feng Gao, Xiaodong Pan, Wei Chen, Peilin Lu, Haining Zhang, Shuting Zhang, Mengya Xing, Qidong Chen, Yue Wang, Zhaozhao Cheng, Yiming Wang, Shilin Zeng, Fang Xie, Yuesong Pan, Yong Shen, Xiaochun Chen, Jiong Shi
Several plasma p-tau217 assays demonstrated strong diagnostic accuracy for amyloid PET positivity in this cross-sectional memory-clinic cohort, although performance varied across platforms and cutoff transferability was limited. Further longitudinal studies with predefined clinical outcomes are needed to determine prognostic value and clinical utility.
BACKGROUND: With the advancement of anti-amyloid treatments for Alzheimer disease, accurate assays for amyloid-β (Aβ) pathology are essential. Plasma phosphorylated tau 217 (p-tau217) is a blood-based biomarker, but its performance varies across platforms, necessitating head-to-head comparisons.
METHODS: This multicenter study evaluated 9 plasma p-tau217 assays (6 including Aβ42 measurements) for detecting amyloid positron emission tomography (PET) positivity. The final analysis included 431 participants from 10 memory clinics in China (median age, 68.0 years; 61.7% women; 64.0% amyloid PET-positive): 30 cognitively unimpaired individuals, 230 with mild cognitive impairment, and 171 with dementia. All plasma samples underwent blinded, batch-matched testing in a central laboratory across chemiluminescence immunoassay (Fujirebio, Beckman, Vazyme, manufacturer A), single-molecule immunoassay (Quanterix, Lychix, iomicsBio, manufacturer B), and multiplex bead-based flow cytometric immunoassay (CellGene).
RESULTS: Seven of the 9 assays showed acceptable performance (area under the curve [AUC] 0.899-0.930), whereas 2 showed lower performance (AUC <0.800; P < 0.001). Under a two-cutoff approach (90% sensitivity/90% specificity), these 7 high-performing assays yielded an intermediate zone of 2.8% to 13.7%. Performance remained robust in mild cognitive impairment and dementia subgroups. Adding Aβ42 showed assay- and population-dependent effects. Manufacturer-recommended and previously published cutoffs showed variable performance in this independent cohort.
CONCLUSIONS: Several plasma p-tau217 assays demonstrated strong diagnostic accuracy for amyloid PET positivity in this cross-sectional memory-clinic cohort, although performance varied across platforms and cutoff transferability was limited. Further longitudinal studies with predefined clinical outcomes are needed to determine prognostic value and clinical utility.