Soelter Tabea M, Whitlock Jordan H, Williams Avery S, Hardigan Andrew A, Lasseigne Brittany N
Department of Cell, Developmental and Integrative Biology, The University of Alabama at Birmingham, AL, USA.
Department of Neurosurgery, Duke University Medical Center, Durham, NC, USA.
Heliyon. 2022 Apr 13;8(4):e09239. doi: 10.1016/j.heliyon.2022.e09239. eCollection 2022 Apr.
Alzheimer's disease (AD) is the most common neurodegenerative disease and affects persons of all races, ethnic groups, and sexes. The disease is characterized by neuronal loss leading to cognitive decline and memory loss. There is no cure and the effectiveness of existing treatments is limited and depends on the time of diagnosis. The long prodromal period, during which patients' ability to live a normal life is not affected despite neuronal loss, often leads to a delayed diagnosis because it can be mistaken for normal aging of the brain. In order to make a substantial impact on AD patient survival, early diagnosis may provide a greater therapeutic window for future therapies to slow AD-associated neurodegeneration. Current gold standards for disease detection include magnetic resonance imaging and positron emission tomography scans, which visualize amyloid β and phosphorylated tau depositions and aggregates. Liquid biopsies, already an active field of research in precision oncology, are hypothesized to provide early disease detection through minimally or non-invasive sample collection techniques. Liquid biopsies in AD have been studied in cerebrospinal fluid, blood, ocular, oral, and olfactory fluids. However, most of the focus has been on blood and cerebrospinal fluid due to biomarker specificity and sensitivity attributed to the effects of the blood-brain barrier and inter-laboratory variation during sample collection. Many studies have identified amyloid β and phosphorylated tau levels as putative biomarkers, however, advances in next-generation sequencing-based liquid biopsy methods have led to significant interest in identifying nucleic acid species associated with AD from liquid tissues. Differences in cell-free RNAs and DNAs have been described as potential biomarkers for AD and hold the potential to affect disease diagnosis, treatment, and future research avenues.
阿尔茨海默病（AD）是最常见的神经退行性疾病，影响所有种族、族裔群体和性别的人群。该疾病的特征是神经元丧失，导致认知能力下降和记忆丧失。目前尚无治愈方法，现有治疗方法的效果有限，且取决于诊断时间。漫长的前驱期，在此期间尽管存在神经元丧失，但患者正常生活的能力并未受到影响，这往往导致诊断延迟，因为它可能被误认为是大脑的正常老化。为了对AD患者的生存产生实质性影响，早期诊断可能为未来减缓AD相关神经退行性变的治疗提供更大的治疗窗口。目前疾病检测的金标准包括磁共振成像和正电子发射断层扫描，这些检查可显示淀粉样β蛋白和磷酸化tau蛋白的沉积和聚集。液体活检在精准肿瘤学领域已是一个活跃的研究领域，据推测它可通过微创或非侵入性样本采集技术实现疾病的早期检测。AD的液体活检已在脑脊液、血液、眼液、口腔液和嗅液中进行了研究。然而，由于血脑屏障的影响以及样本采集过程中的实验室间差异所导致的生物标志物特异性和敏感性，大多数研究集中在血液和脑脊液上。许多研究已将淀粉样β蛋白和磷酸化tau蛋白水平确定为假定的生物标志物，然而，基于下一代测序的液体活检方法的进展引发了人们对从液体组织中识别与AD相关的核酸种类的浓厚兴趣。游离RNA和DNA的差异已被描述为AD的潜在生物标志物，并有可能影响疾病的诊断、治疗及未来的研究方向。
