Chun Min Young, Jang Hyemin, Kim Hee Jin, Kim Jun Pyo, Gallacher John, Allué José Antonio, Sarasa Leticia, Castillo Sergio, Pascual-Lucas María, Na Duk L, Seo Sang Won
Departments of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Department of Neurology, Yonsei University College of Medicine, Seoul, Republic of Korea.
Front Aging Neurosci. 2023 Mar 14;15:1126799. doi: 10.3389/fnagi.2023.1126799. eCollection 2023.
Early detection of β-amyloid (Aβ) accumulation, a major biomarker for Alzheimer's disease (AD), has become important. As fluid biomarkers, the accuracy of cerebrospinal fluid (CSF) Aβ for predicting Aβ deposition on positron emission tomography (PET) has been extensively studied, and the development of plasma Aβ is beginning to receive increased attention recently. In the present study, we aimed to determine whether genotypes, age, and cognitive status increase the predictive performance of plasma Aβ and CSF Aβ levels for Aβ PET positivity.
We recruited 488 participants who underwent both plasma Aβ and Aβ PET studies (Cohort 1) and 217 participants who underwent both cerebrospinal fluid (CSF) Aβ and Aβ PET studies (Cohort 2). Plasma and CSF samples were analyzed using ABtest-MS, an antibody-free liquid chromatography-differential mobility spectrometry-triple quadrupole mass spectrometry method and INNOTEST enzyme-linked immunosorbent assay kits, respectively. To evaluate the predictive performance of plasma Aβ and CSF Aβ, respectively, logistic regression and receiver operating characteristic analyses were performed.
When predicting Aβ PET status, both plasma Aβ42/40 ratio and CSF Aβ42 showed high accuracy (plasma Aβ area under the curve (AUC) 0.814; CSF Aβ AUC 0.848). In the plasma Aβ models, the AUC values were higher than plasma Aβ alone model, when the models were combined with either cognitive stage ( < 0.001) or genotype ( = 0.011). On the other hand, there was no difference between the CSF Aβ models, when these variables were added.
Plasma Aβ might be a useful predictor of Aβ deposition on PET status as much as CSF Aβ, particularly when considered with clinical information such as genotype and cognitive stag.
β-淀粉样蛋白(Aβ)积累是阿尔茨海默病(AD)的主要生物标志物,早期检测变得至关重要。作为体液生物标志物,脑脊液(CSF)Aβ预测正电子发射断层扫描(PET)上Aβ沉积的准确性已得到广泛研究,血浆Aβ的研究近来也开始受到更多关注。在本研究中,我们旨在确定基因型、年龄和认知状态是否会提高血浆Aβ和脑脊液Aβ水平对Aβ PET阳性的预测性能。
我们招募了488名同时接受血浆Aβ和Aβ PET研究的参与者(队列1)以及217名同时接受脑脊液(CSF)Aβ和Aβ PET研究的参与者(队列2)。血浆和脑脊液样本分别使用ABtest-MS(一种无抗体的液相色谱-差分迁移谱-三重四极杆质谱法)和INNOTEST酶联免疫吸附测定试剂盒进行分析。为了分别评估血浆Aβ和脑脊液Aβ的预测性能,进行了逻辑回归和受试者工作特征分析。
在预测Aβ PET状态时,血浆Aβ42/40比值和脑脊液Aβ42均显示出较高的准确性(血浆Aβ曲线下面积(AUC)为0.814;脑脊液Aβ AUC为0.848)。在血浆Aβ模型中,当模型与认知阶段(<0.001)或基因型(=0.011)相结合时,AUC值高于单独血浆Aβ模型。另一方面,添加这些变量后,脑脊液Aβ模型之间没有差异。
血浆Aβ可能与脑脊液Aβ一样,是PET状态下Aβ沉积的有用预测指标,特别是在结合基因型和认知阶段等临床信息时。