MicroRNAs in tear fluids predict underlying molecular changes associated with Alzheimer's disease.
MicroRNAs in tear fluids predict underlying molecular changes associated with Alzheimer's disease.
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DOI：
10.26508/lsa.202201757
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发表时间：
2023-06
影响因子：
4.4
通讯作者：
Matsubara, Joanne A.
中科院分区：
文献类型：
--
作者：
Wijesinghe, Printha;Xi, Jeanne;Cui, Jing;Campbell, Matthew;Pham, Wellington;Matsubara, Joanne A.
这项研究证明了在转基因AD小鼠模型中，去调节的泪液miRNAs与淀粉样β蛋白的产生和前炎症相关的翻译潜力。细胞外循环microRNAs(MiRNAs)已被认为是阿尔茨海默病(AD)诊断的潜在生物标志物。由于视网膜是中枢神经系统的一部分，我们假设在AD进展的不同阶段，大脑，特别是新皮质-海马体、眼组织和泪液中miRNAs的表达水平相似。在年轻和老年的转基因APP-PS1小鼠、非携带者同胞和C57BL/6J野生型对照鼠中，对10个miRNA候选进行了系统的研究。与年龄和性别匹配的野生型对照相比，测试的miRNAs的相对表达水平在APP-PS1小鼠和非携带者兄弟姐妹中显示出类似的模式。然而，APP-PS1小鼠和非携带者兄弟姐妹之间的表达水平差异可能是AD潜在的分子病因学造成的。重要的是，与淀粉样β蛋白(Aβ)产生(-101a、-15a和-342)和前炎症(-125b、-146a和-34a)相关的miRNA显示，随着疾病的进展，泪液中β显著上调，正如皮质A miRNA负荷和反应性星形胶质细胞增生症所跟踪的那样。总体而言，首次全面证明了上调的泪液miRNAs与AD发病机制相关的翻译潜力。
This study demonstrated the translational potential of deregulated tear fluid miRNAs associated with amyloid beta production and proinflammation in a transgenic AD mouse model. Extracellular circulating microRNAs (miRNAs) have been discussed as potential biomarkers for Alzheimer’s disease (AD) diagnosis. As the retina is a part of the CNS, we hypothesize that miRNAs expression levels in the brain, particularly neocortex–hippocampus, eye tissues, and tear fluids are similar at different stages of AD progression. Ten miRNA candidates were systematically investigated in transgenic APP-PS1 mice, noncarrier siblings, and C57BL/6J wild-type controls at young and old ages. Relative expression levels of tested miRNAs revealed a similar pattern in both APP-PS1 mice and noncarrier siblings when compared with age- and sex-matched wild-type controls. However, the differences seen in expression levels between APP-PS1 mice and noncarrier siblings could possibly have resulted from underlying molecular etiology of AD. Importantly, miRNAs associated with amyloid beta (Aβ) production (-101a, -15a, and -342) and proinflammation (-125b, -146a, and -34a) showed significant up-regulations in the tear fluids with disease progression, as tracked by cortical Aβ load and reactive astrogliosis. Overall, for the first time, the translational potential of up-regulated tear fluid miRNAs associated with AD pathogenesis was comprehensively demonstrated.
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