DiamiR, LLC Princeton, NJ, USA.
Front Cell Neurosci. 2013 Sep 10;7:150. doi: 10.3389/fncel.2013.00150.
Many neurodegenerative diseases, such as Alzheimer's disease, Parkinson disease, vascular and frontotemporal dementias, as well as other chronic neurological pathologies, are characterized by slow development with a long asymptomatic period followed by a stage with mild clinical symptoms. As a consequence, these serious pathologies are diagnosed late in the course of a disease, when massive death of neurons has already occurred and effective therapeutic intervention is problematic. Thus, the development of screening tests capable of detecting neurodegenerative diseases during early, preferably asymptomatic, stages is a high unmet need. Since such tests are to be used for screening of large populations, they should be non-invasive and relatively inexpensive. Further, while subjects identified by screening tests can be further tested with more invasive and expensive methods, e.g., analysis of cerebrospinal fluid or imaging techniques, to be of practical utility screening tests should have high sensitivity and specificity. In this review, we discuss advantages and disadvantages of various approaches to developing screening tests based on analysis of circulating cell-free microRNA (miRNA). Applications of circulating miRNA-based tests for diagnosis of acute and chronic brain pathologies, for research of normal brain aging, and for disease and treatment monitoring are also discussed.
许多神经退行性疾病,如阿尔茨海默病、帕金森病、血管性和额颞叶痴呆以及其他慢性神经病理学疾病,其特征是发展缓慢,有一个很长的无症状期,随后是一个有轻微临床症状的阶段。因此,这些严重的病理在疾病的晚期才被诊断出来,此时神经元已经大量死亡,有效的治疗干预变得困难。因此,开发能够在早期(最好是无症状)阶段检测神经退行性疾病的筛查测试是一个巨大的未满足的需求。由于这些测试将用于对大量人群进行筛查,因此它们应该是非侵入性的和相对便宜的。此外,虽然筛选测试确定的受试者可以用更具侵入性和昂贵的方法进一步测试,例如脑脊液分析或成像技术,但为了具有实际效用,筛选测试应该具有高灵敏度和特异性。在这篇综述中,我们讨论了基于循环无细胞 microRNA(miRNA)分析开发筛查测试的各种方法的优缺点。还讨论了循环 miRNA 测试在急性和慢性脑病理学诊断、正常脑衰老研究以及疾病和治疗监测中的应用。