Fully automated and highly specific plasma β-amyloid immunoassays predict β-amyloid status defined by amyloid positron emission tomography with high accuracy

Alzheimer’s Research & Therapy

Shobha Dhadda¹  David Verbel²  Yuji Arimatsu³  Kei Hagino³  Junko Kawahira³  Yasuhiro Irino⁴  Kazuto Yamashita⁴  Toshiyuki Sato⁴  Shunsuke Watanabe⁴  Kengo Ishiki⁴  Shigeki Iwanaga⁴  Masahiro Miura⁴  Atsushi Iwata⁵  Kota Nagai⁶  Hayato Niiro⁷  Katsutaka Sasaki⁸  Takayuki Arai⁸  Tomokazu Yoshida⁹  Toshiko Kubo^1,10  Akihiko Koyama^1,11 

[1] Biostatistics and Project Operations, Eisai Inc.;Biostatistics, Eisai Inc.;Business Incubation Division, Sysmex Corporation;Central Research Laboratories, Sysmex Corporation;Department of Neurology, Tokyo Metropolitan Geriatric Hospital;Japan and Asia Clinical Development Department, Eisai Co., Ltd.;Medical Affairs Division, Sysmex Corporation;Reagent Engineering Division, Sysmex Corporation;Sysmex Corporation;Sysmex R&D Center Americas, Inc.;Translational Science, Eisai Inc.;

关键词: Alzheimer’s disease;    Beta-amyloid;    Biomarker;    Diagnosis;    Immunoassay;    Plasma;   

DOI  :  10.1186/s13195-022-01029-0

来源: DOAJ

【 摘 要 】

Abstract Background Clinicians, researchers, and patients alike would greatly benefit from more accessible and inexpensive biomarkers for neural β-amyloid (Aβ). We aimed to assess the performance of fully automated plasma Aβ immunoassays, which correlate significantly with immunoprecipitation mass spectrometry assays, in predicting brain Aβ status as determined by visual read assessment of amyloid positron emission tomography (PET). Methods The plasma Aβ42/Aβ40 ratio was measured using a fully automated immunoassay platform (HISCL series) in two clinical studies (discovery and validation studies). The discovery and validation sample sets were retrospectively and randomly selected from participants with early Alzheimer’s disease (AD) identified during screening for the elenbecestat Phase 3 program. Results We included 197 participants in the discovery study (mean [SD] age 71.1 [8.5] years; 112 females) and 200 in the validation study (age 70.8 [7.9] years; 99 females). The plasma Aβ42/Aβ40 ratio predicted amyloid PET visual read status with areas under the receiver operating characteristic curves of 0.941 (95% confidence interval [CI] 0.910–0.973) and 0.868 (95% CI 0.816–0.920) in the discovery and validation studies, respectively. In the discovery study, a cutoff value of 0.102 was determined based on maximizing the Youden Index, and the sensitivity and specificity were calculated to be 96.0% (95% CI 90.1–98.9%) and 83.5% (95% CI 74.6–90.3%), respectively. Using the same cutoff value, the sensitivity and specificity in the validation study were calculated to be 88.0% (95% CI 80.0–93.6%) and 72.0% (95% CI 62.1–80.5%), respectively. Conclusions The plasma Aβ42/Aβ40 ratio measured using the HISCL series achieved high accuracy in predicting amyloid PET status. Since our blood-based immunoassay system is less invasive and more accessible than amyloid PET and cerebrospinal fluid testing, it may contribute to the diagnosis of AD in routine clinical practice.

【 授权许可】

Unknown