C 2 N Diagnostics, St Louis, Missouri.
Departments of Neurology, Radiology & Biomedical Imaging, University of California, San Francisco.
JAMA Netw Open. 2022 Apr 1;5(4):e228392. doi: 10.1001/jamanetworkopen.2022.8392.
The diagnostic evaluation for Alzheimer disease may be improved by a blood-based diagnostic test identifying presence of brain amyloid plaque pathology.
To determine the clinical performance associated with a diagnostic algorithm incorporating plasma amyloid-β (Aβ) 42:40 ratio, patient age, and apoE proteotype to identify brain amyloid status.
DESIGN, SETTING, AND PARTICIPANTS: This cohort study includes analysis from 2 independent cross-sectional cohort studies: the discovery cohort of the Plasma Test for Amyloidosis Risk Screening (PARIS) study, a prospective add-on to the Imaging Dementia-Evidence for Amyloid Scanning study, including 249 patients from 2018 to 2019, and MissionAD, a dataset of 437 biobanked patient samples obtained at screenings during 2016 to 2019. Data were analyzed from May to November 2020.
Amyloid detected in blood and by positron emission tomography (PET) imaging.
The main outcome was the diagnostic performance of plasma Aβ42:40 ratio, together with apoE proteotype and age, for identifying amyloid PET status, assessed by accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC).
All 686 participants (mean [SD] age 73.2 [6.3] years; 368 [53.6%] men; 378 participants [55.1%] with amyloid PET findings) had symptoms of mild cognitive impairment or mild dementia. The AUC of plasma Aβ42:40 ratio for PARIS was 0.79 (95% CI, 0.73-0.85) and 0.86 (95% CI, 0.82-0.89) for MissionAD. Ratio cutoffs for Aβ42:40 based on the Youden index were similar between cohorts (PARIS: 0.089; MissionAD: 0.092). A logistic regression model (LRM) incorporating Aβ42:40 ratio, apoE proteotype, and age improved diagnostic performance within each cohort (PARIS: AUC, 0.86 [95% CI, 0.81-0.91]; MissionAD: AUC, 0.89 [95% CI, 0.86-0.92]), and overall accuracy was 78% (95% CI, 72%-83%) for PARIS and 83% (95% CI, 79%-86%) for MissionAD. The model developed on the prospectively collected samples from PARIS performed well on the MissionAD samples (AUC, 0.88 [95% CI, 0.84-0.91]; accuracy, 78% [95% CI, 74%-82%]). Training the LRM on combined cohorts yielded an AUC of 0.88 (95% CI, 0.85-0.91) and accuracy of 81% (95% CI, 78%-84%). The output of this LRM is the Amyloid Probability Score (APS). For clinical use, 2 APS cutoff values were established yielding 3 categories, with low, intermediate, and high likelihood of brain amyloid plaque pathology.
These findings suggest that this blood biomarker test could allow for distinguishing individuals with brain amyloid-positive PET findings from individuals with amyloid-negative PET findings and serve as an aid for Alzheimer disease diagnosis.
通过一种能够识别脑淀粉样斑块病理的基于血液的诊断测试，阿尔茨海默病的诊断评估可能会得到改善。
确定与包含血浆淀粉样蛋白-β（Aβ）42:40 比值、患者年龄和载脂蛋白 E 表型的诊断算法相结合的临床性能，以识别脑淀粉样状态。
设计、地点和参与者：这项队列研究包括来自 2 项独立横断面队列研究的分析：血浆淀粉样蛋白风险筛查试验（PARIS）的发现队列，是对成像痴呆-淀粉样扫描证据的前瞻性附加研究，包括 2018 年至 2019 年的 249 名患者，以及 MissionAD，这是一个在 2016 年至 2019 年筛查期间获得的 437 个生物样本数据集。数据分析于 2020 年 5 月至 11 月进行。
血液中以及正电子发射断层扫描（PET）成像中检测到的淀粉样蛋白。
主要结果是血浆 Aβ42:40 比值与 apoE 表型和年龄相结合，用于确定淀粉样 PET 状态的诊断性能，通过准确性、敏感性、特异性和接受者操作特征曲线（ROC）下的面积（AUC）进行评估。
所有 686 名参与者（平均[标准差]年龄 73.2[6.3]岁；368[53.6%]名男性；378 名参与者[55.1%]有淀粉样 PET 发现）有轻度认知障碍或轻度痴呆的症状。PARIS 的血浆 Aβ42:40 比值 AUC 为 0.79（95%CI，0.73-0.85），而 MissionAD 的 AUC 为 0.86（95%CI，0.82-0.89）。基于约登指数的 Aβ42:40 比值截断值在两个队列中相似（PARIS：0.089；MissionAD：0.092）。纳入 Aβ42:40 比值、apoE 表型和年龄的逻辑回归模型（LRM）提高了每个队列的诊断性能（PARIS：AUC，0.86[95%CI，0.81-0.91]；MissionAD：AUC，0.89[95%CI，0.86-0.92]），整体准确性为 78%（95%CI，72%-83%），PARIS 为 83%（95%CI，79%-86%）。在 PARIS 前瞻性收集的样本上开发的模型在 MissionAD 样本上表现良好（AUC，0.88[95%CI，0.84-0.91]；准确性，78%[95%CI，74%-82%]）。在联合队列上训练 LRM 得到 AUC 为 0.88（95%CI，0.85-0.91）和 81%（95%CI，78%-84%）的准确性。该 LRM 的输出是淀粉样蛋白概率评分（APS）。为了临床应用，建立了 2 个 APS 截断值，产生了 3 个类别，具有脑淀粉样斑块病理的低、中和高度可能性。
这些发现表明，这种血液生物标志物测试可以区分具有脑淀粉样蛋白阳性 PET 发现的个体与具有淀粉样蛋白阴性 PET 发现的个体，并有助于阿尔茨海默病的诊断。
