Establishment and verification of reference intervals for Alzheimer's disease plasma biomarkers based on evaluation of pre‐analytical procedures: a multicenter study

作者：Wencan Jiang, Jialong Liu, Wu Yuan, Jing Li, Jin He, Zixin Cui, Ximeng Chen, Tenghong Lian, Hong Lv, Bingqing Han, Dandan Yu, Chenxu Wang, Guoge Li, Kelin Chen, Siwen Li, Lijuan Wang, Wei Zhang, Rong Wang, Guojun Zhang · 发表于：Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · 年份：2025 · DOI：10.1002/dad2.70194 · 被引用次数：1 · 研究领域：Clinical Laboratory Practices and Quality Control、Dementia and Cognitive Impairment Research、Sepsis Diagnosis and Treatment

Abstract INTRODUCTION To establish and verify reference intervals (RIs) for Alzheimer's disease (AD) plasma biomarkers amyloid beta (Aβ) 40, Aβ42, phosphorylated tau 181 (p‐tau181), p‐tau217, and total tau (t‐tau) after defining optimal pre‐analytical procedures. METHODS Pre‐analytical procedures were assessed, including storage of whole blood and plasma under different conditions and freeze‐thaw times. RIs were established using 738 samples, with grouping by sex and age (≤ 44, 45 to 59, ≥60 years), and verified with 120 samples from four clinical centers. RESULTS Samples stored at 2°C to 8°C for 22 to 28 h or −20°C to −80°C for 30 days were stable. Though sex/age differences in biomarker levels existed, they did not require partitioning. RIs of Aβ40, Aβ42, p‐tau181, p‐tau217, and t‐tau were 12.71 to 283.6, 2.313 to 25.96, 0.8342 to 18.36, 0.3351 to 4.310, and 0.8096 to 18.65 pg/mL, respectively. The verification rates of RIs with the multicenter cohort ( n = 120) were 93.33% to 99.14%. DISCUSSION The established RIs for Chinese adults can potentially facilitate the early diagnosis of AD. Highlights Optimized pre‐analytical procedures: Plasma levels of Aβ40, Aβ42, p‐tau181, p‐tau217, and t‐tau are unstable at room temperature (25 ± 3°C) but remain stable for 22 to 28 h at 2°C to 8°C (fluctuation ≤10%). For long‐term storage, −20°C to −80°C is suitable, with stability maintained for 30 days; ≤5 freeze‐thaw cycles have minimal impact on biomarker levels. Established reference i...