Jang Hyemin, Kim Ji Sun, Lee Hye Joo, Kim Chi-Hun, Na Duk L, Kim Hee Jin, Allué José Antonio, Sarasa Leticia, Castillo Sergio, Pesini Pedro, Gallacher John, Seo Sang Won
Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea.
Neuroscience Center, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea.
Alzheimers Res Ther. 2021 Oct 22;13(1):179. doi: 10.1186/s13195-021-00911-7.
We assessed the feasibility of plasma Aβ42/Aβ40 determined using a novel liquid chromatography-mass spectrometry method (LC-MS) as a useful biomarker of PET status in a Korean cohort from the DPUK Study.
A total of 580 participants belonging to six groups, Alzheimer's disease dementia (ADD, n = 134), amnestic mild cognitive impairment (aMCI, n = 212), old controls (OC, n = 149), young controls (YC, n = 15), subcortical vascular cognitive impairment (SVCI, n = 58), and cerebral amyloid angiopathy (CAA, n = 12), were included in this study. Plasma Aβ40 and Aβ42 were quantitated using a new antibody-free, LC-MS, which drastically reduced the sample preparation time and cost. We performed receiver operating characteristic (ROC) analysis to develop the cutoff of Aβ42/Aβ40 and investigated its performance predicting centiloid-based PET positivity (PET+).
Plasma Aβ42/Aβ40 were lower for PET+ individuals in ADD, aMCI, OC, and SVCI (p < 0.001), but not in CAA (p = 0.133). In the group of YC, OC, aMCI, and ADD groups, plasma Aβ42/Aβ40 predicted PET+ with an area under the ROC curve (AUC) of 0.814 at a cutoff of 0.2576. When adding age, APOE4, and diagnosis, the AUC significantly improved to 0.912.
Plasma Aβ42/Aβ40, as measured by this novel LC-MS method, showed good discriminating performance based on PET positivity.
我们评估了使用一种新型液相色谱-质谱法（LC-MS）测定血浆Aβ42/Aβ40作为来自DPUK研究的韩国队列中PET状态有用生物标志物的可行性。
本研究纳入了总共580名参与者，分为六组，即阿尔茨海默病痴呆（ADD，n = 134）、遗忘型轻度认知障碍（aMCI，n = 212）、老年对照组（OC，n = 149）、青年对照组（YC，n = 15）、皮质下血管性认知障碍（SVCI，n = 58）和脑淀粉样血管病（CAA，n = 12）。使用一种新的无抗体LC-MS对血浆Aβ40和Aβ42进行定量，这大大减少了样品制备时间和成本。我们进行了受试者工作特征（ROC）分析以确定Aβ42/Aβ40的临界值，并研究其预测基于百分位数的PET阳性（PET+）的性能。
ADD、aMCI、OC和SVCI组中PET+个体的血浆Aβ42/Aβ40较低（p < 0.001），但CAA组中并非如此（p = 0.133）。在YC、OC、aMCI和ADD组中，血浆Aβ42/Aβ40在临界值为0.2576时预测PET+的受试者工作特征曲线下面积（AUC）为0.814。当加入年龄、APOE4和诊断因素时，AUC显著提高至0.912。
通过这种新型LC-MS方法测量的血浆Aβ42/Aβ40基于PET阳性显示出良好的鉴别性能。
