Ultrasensitive Detection of Plasma Amyloid-β as a Biomarker for Cognitively Normal Elderly Individuals at Risk of Alzheimer's Disease
Ultrasensitive Detection of Plasma Amyloid-β as a Biomarker for Cognitively Normal Elderly Individuals at Risk of Alzheimer's Disease
复制标题
DOI：
10.3233/jad-190533
复制
发表时间：
2019-01-01
影响因子：
4
通讯作者：
Martins, Ralph N.
中科院分区：
文献类型：
--
作者：
Chatterjee, Pratishtha;Elmi, Mitra;Martins, Ralph N.
背景：大脑中异常的淀粉样蛋白β（β）沉积发生在阿尔茨海默氏病（AD）临床症状之前的二十年之前，因此大脑是使用PET作为金标准生物标志物测量的β载荷，用于AD的早期诊断。然而，宠物的不经济性质使血液标记物反映了大脑的beta沉积，有吸引力的候选者作为替代标记物进行调查。目标：血浆研究βAβ作为大脑的替代标志物，是brain的替代标记，是老年人的认知正常个体中的beta beta。在95个认知正常的老年人中，使用超敏感的单分子阵列（SIMOA）测定测量血浆Aβ（40）和β（42）浓度，他们都经历了宠物来评估大脑ββ沉积。基于使用示踪剂F-18-forbetaben获得的标准摄取值比（SUVR），比较了32名参与者在评估的32名参与者之间比较了Beta的beta（beta-，suvr = 1.35）。结果：与A BetA组相比，A Beta+组的血浆Aβ（42）/Aβ（40）比率较低。尽管在A beta+组中观察到较高的血浆Aβ（40）趋势，但血浆A Beta（40）和BetA（42）水平在β-和A BetA组之间没有显着差异。此外，等离子体A Beta（42）/A Beta（40）比率以及已知的AD风险因素，年龄和APOE Epsilon 4状态，导致beta+参与者与基于接收器操作的区域下的区域的β参与者区分开特征曲线显示为78％。结论：血浆中的beta比率是大脑的潜在生物标志物Aβ沉积，因此是临床前AD。但是，测量血浆的方法需要进一步开发，以提高这种有希望的AD血液生物标志物的准确性。
Background: Aberrant amyloid-beta (A beta) deposition in the brain occurs two decades prior to the manifestation of Alzheimer's disease (AD) clinical symptoms and therefore brain A beta load measured using PET serves as a gold standard biomarker for the early diagnosis of AD. However, the uneconomical nature of PET makes blood markers, that reflect brain A beta deposition, attractive candidates for investigation as surrogate markers.Objective: Investigation of plasma A beta as a surrogate marker for brain A beta deposition in cognitively normal elderly individuals.Methods: Plasma A beta(40) and A beta(42) concentrations were measured using the ultrasensitive Single Molecule Array (Simoa) assay in 95 cognitively normal elderly individuals, who have all undergone PET to assess brain A beta deposition. Based on the standard uptake value ratios (SUVR) obtained from PET imaging, using the tracer F-18-Florbetaben, plasma A beta was compared between 32 participants assessed to have low brain A beta load (A beta-, SUVR = 1.35).Results: Plasma A beta(42)/A beta(40) ratios were lower in the A beta+ group compared to the A beta- group. Plasma A beta(40) and A beta(42) levels were not significantly different between A beta- and A beta+ groups, although a trend of higher plasma A beta(40) was observed in the A beta+ group. Additionally, plasma A beta(42)/A beta(40) ratios along with the known AD risk factors, age and APOE epsilon 4 status, resulted in A beta+ participants being distinguished from A beta- participants based on an area under the receiver operating characteristic curve shown to be 78%.Conclusion: Plasma A beta ratios in this study are a potential biomarker for brain A beta deposition and therefore, for preclinical AD. However, this method to measure plasma A beta needs further development to increase the accuracy of this promising AD blood biomarker.