Plasma amyloid assay as a pre-screening tool for amyloid positron emission tomography imaging in early stage Alzheimer's disease
Plasma amyloid assay as a pre-screening tool for amyloid positron emission tomography imaging in early stage Alzheimer's disease
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DOI：
10.1186/s13195-019-0566-0
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发表时间：
2019-12-27
影响因子：
9
通讯作者：
Wang, Pei-Ning
中科院分区：
文献类型：
--
作者：
Lin, Szu-Ying;Lin, Kun-Ju;Wang, Pei-Ning
引言由于确定早期阿尔茨海默病（AD）患者的淀粉样蛋白正电子发射断层扫描（PET+）阳性的高成本和高失败率，需要一种有效的淀粉样蛋白PET扫描的预筛选工具。方法轻度认知功能障碍（n = 33，PET+24.2%，女性42%，年龄74.4 ± 7.5，MMSE 26.8 ± 1.9）和轻度痴呆（n = 19，PET+63.6%，女性36.3%，年龄73.0 ± 9.3，MMSE 22.6 ± 2.0）患者入选。进行淀粉样蛋白PET成像、载脂蛋白E（APOE）基因分型、血浆淀粉样蛋白β（A β）（1-40）、A β（1-42）和免疫磁性还原（IMR）法总tau蛋白定量。进行受试者操作特征（ROC）分析和尤登指数以确定可能的截止点、临床敏感性/特异性和曲线下面积（AUC）。结果淀粉样蛋白PET+受试者的血浆A β（1-42）水平低于淀粉样蛋白PET阴性（PET-）受试者。APOE β 4携带者的血浆A β（1-42）高于非携带者。我们开发了一种涉及血浆A β（1-42）和APOE基因分型组合的算法。在临床疑似MCI和轻度痴呆患者中，有效检测淀粉样蛋白PET+患者的成功率从42.3%增加到70.4%。结论APOE基因型联合血浆A β（1-42）水平可作为预测早期痴呆患者淀粉样蛋白PET阳性的预筛选工具。
Introduction Due to the high cost and high failure rate of ascertaining amyloid positron emission tomography positivity (PET+) in patients with earlier stage Alzheimer's disease (AD), an effective pre-screening tool for amyloid PET scans is needed. Methods Patients with mild cognitive impairment (n = 33, 24.2% PET+, 42% females, age 74.4 +/- 7.5, MMSE 26.8 +/- 1.9) and mild dementia (n = 19, 63.6% PET+, 36.3% females, age 73.0 +/- 9.3, MMSE 22.6 +/- 2.0) were recruited. Amyloid PET imaging, Apolipoprotein E (APOE) genotyping, and plasma amyloid beta (A beta)(1-40), A beta(1-42), and total tau protein quantification by immunomagnetic reduction (IMR) method were performed. Receiver operating characteristics (ROC) analysis and Youden's index were performed to identify possible cut-off points, clinical sensitivities/specificities, and areas under the curve (AUCs). Results Amyloid PET+ participants had lower plasma A beta(1-42) levels than amyloid PET-negative (PET-) subjects. APOE epsilon 4 carriers had higher plasma A beta(1-42) than non-carriers. We developed an algorithm involving the combination of plasma A beta(1-42) and APOE genotyping. The success rate for detecting amyloid PET+ patients effectively increased from 42.3 to 70.4% among clinically suspected MCI and mild dementia patients. Conclusions Our results demonstrate the possibility of utilizing APOE genotypes in combination with plasma A beta(1-42) levels as a pre-screening tool for predicting the positivity of amyloid PET findings in early stage dementia patients.