Nucleic acid liquid biopsies in Alzheimer's disease: current state, challenges, and opportunities.
Nucleic acid liquid biopsies in Alzheimer's disease: current state, challenges, and opportunities.
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DOI：
10.1016/j.heliyon.2022.e09239
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发表时间：
2022-04
期刊：
影响因子：
4
通讯作者：
Lasseigne, Brittany N.
中科院分区：
文献类型：
--
作者：
Soelter, Tabea M.;Whitlock, Jordan H.;Williams, Avery S.;Hardigan, Andrew A.;Lasseigne, Brittany N.
关键词：
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、民族和性别的人。该疾病的特征是神经元丧失，导致认知能力下降和记忆力丧失。没有治愈方法，现有治疗方法的有效性有限，并取决于诊断时间。长的前驱期，在此期间，尽管神经元损失，患者过正常生活的能力不受影响，但往往导致诊断延迟，因为它可能被误认为是大脑的正常老化。为了对AD患者的生存率产生实质性影响，早期诊断可能为未来的治疗提供更大的治疗窗口，以减缓AD相关的神经退行性变。目前用于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，其可视化淀粉样蛋白β和磷酸化tau沉积和聚集体。液体活检，已经是精确肿瘤学的一个活跃的研究领域，被假设为通过微创或非侵入性样本采集技术提供早期疾病检测。AD的液体活检已在脑脊液、血液、眼、口腔和嗅觉液中进行了研究。然而，由于血脑屏障的影响和样本采集期间实验室间差异导致的生物标志物特异性和敏感性，大部分关注点都集中在血液和脑脊液上。许多研究已经将淀粉样蛋白β和磷酸化tau水平鉴定为推定的生物标志物，然而，基于下一代测序的液体活检方法的进展已经导致对从液体组织中鉴定与AD相关的核酸种类的极大兴趣。无细胞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，治疗和未来的研究途径。液体活检;循环生物标志物;阿尔茨海默病;神经变性;无细胞;诊断。
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. Liquid biopsy; Circulating biomarkers; Alzheimer's disease; Neurodegeneration; Cell-free; Diagnosis.
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