Peripheral Biomarkers for Alzheimer's Disease: Update and Progress.
Peripheral Biomarkers for Alzheimer's Disease: Update and Progress.
复制标题
阿尔茨海默病的外周生物标志物：更新和进展。
DOI：
10.1007/s40120-019-00171-6
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发表时间：
2019
影响因子：
3.7
通讯作者：
Blennow,Kaj
中科院分区：
文献类型：
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作者：
Sabbagh,MarwanN;Blennow,Kaj
1984年，NINDS-ADRDA公布了标准，指出明确的阿尔茨海默病（AD）只能通过活检或尸检确认[1]。该出版物导致广泛认为AD诊断仅为排除诊断。从那时起，该领域随着具有高灵敏度和特异性的脑脊液（CSF）检测AD的出现而迅速发展[2]，以及淀粉样蛋白正电子发射断层扫描（PET）、tau PET和氟脱氧葡萄糖PET的发展。淀粉样蛋白PET已成为一种可能改变临床管理的附加值检测[3，4]。磁共振成像（MRI）也正在发展成为一种测量区域体积的工具，特别是在海马体内，作为神经退行性变的替代指标。这些测试中的许多具有优异的特异性和灵敏度，但受限于诸如PET的技术的获取/可用性、测试的费用以及腰椎穿刺的侵入性质量。理想情况下，外周生物标志物可以用作筛查工具，其驱动因素是阴性预测值，类似于淀粉样蛋白PET成像。这种类型的生物标志物将是有利的，因为它的最小侵入性和潜在的较低成本。具体而言，具有正常值的外周诊断工具将反映不存在目标病理，而异常值将提示使用PET和MR成像技术或CSF测试进行进一步调查。它可以作为治疗和预防试验中的筛选工具，并大大降低排除没有目标病理的潜在参与者的成本。当疾病改善疗法可用时，筛查测试在初级保健环境中也是有价值的。近年来，对外周生物标志物的开发的探索迅速加速。这种加速部分是由于技术发展，超灵敏方法将定量下限从纳克/升范围降低到皮克/升范围。因此，以前被认为在外周样本中检测不到的蛋白质现在可以测量。在这个特殊的问题，我们包括七个创新的和潜在的可扩展的外围诊断测试目前正在开发中。
In 1984, the NINDS-ADRDA published criteria stating that definite Alzheimer’s disease (AD) could only be confirmed by biopsy or autopsy [1]. This publication led to the widely held perception that AD diagnosis was a diagnosis of exclusion only. Since then, the field has evolved rapidly with the advent of cerebrospinal fluid (CSF) testing for AD with great sensitivity and specificity [2], and the development of amyloid positron emission tomography (PET), tau PET, and fluorodeoxyglucose PET. Amyloid PET has emerged as an added value test that could alter clinical management [3, 4]. Magnetic resonance imaging (MRI) is also evolving as a tool to measure regional volumes, particularly within the hippocampus, as a proxy measure of neurodegeneration. Many of these tests have excellent specificity and sensitivity but are limited by access/availability of such technologies as PET, the expense of tests, and the invasive quality of lumbar puncture. Ideally, a peripheral biomarker could be used as a screening tool, with the driver being the negative predictive value, similar to amyloid PET imaging. This type of biomarker would be advantageous for its minimal invasiveness and potentially lower cost. Specifically, a peripheral diagnostic tool with a normal value would reflect the absence of the target pathology, while an abnormal value would prompt further investigation using PET and MR imaging techniques, or CSF tests. It could be valuable as a screening tool in therapeutic and prevention trials and considerably reduce the costs of ruling out potential participants who do not have the target pathology. Screening tests also would be valuable in the primary care setting when disease-modifying therapies become available. Exploration into the development of peripheral biomarkers has accelerated rapidly in recent years. This acceleration is partly due to technological developments, with ultra-sensitive methods lowering the lower limit of quantification from the nanogram per liter range to the picogram per liter range. Thus, proteins previously thought to be undetectable in peripheral samples are now measurable. In this special issue, we include seven innovative and potentially scalable peripheral diagnostic tests currently in development.