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基于组学的生物标志物用于早期阿尔茨海默病诊断和可靠治疗靶点开发。

Omics-based Biomarkers for the Early Alzheimer Disease Diagnosis and Reliable Therapeutic Targets Development.

机构信息

Neonatal Research Unit, Health Research Institute La Fe, Valencia, Spain.

Neurology Unit, University and Polytechnic Hospital La Fe, Valencia, Spain.

出版信息

Curr Neuropharmacol. 2019;17(7):630-647. doi: 10.2174/1570159X16666180926123722.

Abstract

BACKGROUND

Alzheimer's disease (AD), the most common cause of dementia in adulthood, has great medical, social, and economic impact worldwide. Available treatments result in symptomatic relief, and most of them are indicated from the early stages of the disease. Therefore, there is an increasing body of research developing accurate and early diagnoses, as well as diseasemodifying therapies.

OBJECTIVE

Advancing the knowledge of AD physiopathological mechanisms, improving early diagnosis and developing effective treatments from omics-based biomarkers.

METHODS

Studies using omics technologies to detect early AD, were reviewed with a particular focus on the metabolites/lipids, micro-RNAs and proteins, which are identified as potential biomarkers in non-invasive samples.

RESULTS

This review summarizes recent research on metabolomics/lipidomics, epigenomics and proteomics, applied to early AD detection. Main research lines are the study of metabolites from pathways, such as lipid, amino acid and neurotransmitter metabolisms, cholesterol biosynthesis, and Krebs and urea cycles. In addition, some microRNAs and proteins (microglobulins, interleukins), related to a common network with amyloid precursor protein and tau, have been also identified as potential biomarkers. Nevertheless, the reproducibility of results among studies is not good enough and a standard methodological approach is needed in order to obtain accurate information.

CONCLUSION

The assessment of metabolomic/lipidomic, epigenomic and proteomic changes associated with AD to identify early biomarkers in non-invasive samples from well-defined participants groups will potentially allow the advancement in the early diagnosis and improvement of therapeutic interventions.

摘要

背景

阿尔茨海默病(AD)是成年期最常见的痴呆症病因,在全球范围内具有重大的医疗、社会和经济影响。现有的治疗方法仅能缓解症状,且大多数治疗方法都适用于疾病早期。因此,越来越多的研究致力于开发准确、早期的诊断方法和疾病修饰疗法。

目的

深入了解 AD 的病理生理机制,提高早期诊断水平,并基于组学标志物开发有效的治疗方法。

方法

对使用组学技术来检测早期 AD 的研究进行了综述,特别关注了在非侵入性样本中被鉴定为潜在生物标志物的代谢物/脂质、micro-RNAs 和蛋白质。

结果

本综述总结了代谢组学/脂质组学、表观基因组学和蛋白质组学在早期 AD 检测中的最新研究进展。主要研究方向是研究与脂质、氨基酸和神经递质代谢、胆固醇生物合成以及克雷布斯和尿素循环等途径相关的代谢物。此外,还鉴定了一些与淀粉样前体蛋白和 tau 相关的 microRNAs 和蛋白质(微球蛋白、白细胞介素)作为潜在的生物标志物。然而,研究之间的结果重现性还不够好,需要采用标准的方法学方法来获取准确的信息。

结论

评估与 AD 相关的代谢组学/脂质组学、表观基因组学和蛋白质组学变化,以在明确界定的参与者组中从非侵入性样本中识别早期生物标志物,将有可能促进早期诊断的发展并改善治疗干预措施。

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