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miRNA-483-5p 作为阿尔茨海默病早期检测的潜在非侵入性生物标志物。

MiRNA -483-5p as a Potential Noninvasive Biomarker for Early Detection of Alzheimer's Disease.

机构信息

Clinical Pathology Department, Faculty of Medicine for Girls, AL-Azhar University, Cairo, Egypt.

Neurology Department, Faculty of Medicine for Girls, AL-Azhar University ,Cairo, Egypt.

出版信息

Egypt J Immunol. 2020 Jun;27(2):59-72.

PMID:33548978
Abstract

Alzheimer's disease (AD) is an irreversible, progressive neurodegenerative disease that accounts for 62% of dementia cases in elderly. Early diagnosis of AD is crucial for successful treatment in order to slow disease progression and avoid deterioration. Current diagnostic tools for AD are unable to detect the disease in its early stage; in addition, they still have several limitations. Many studies have shown that microRNAs (miRNAs) are implicated in the pathogenesis of AD, and alterations of their levels in blood make them potential biomarkers for AD. We aimed to evaluate the plasma microRNA-483-5p as a non -invasive biomarker for early diagnosis of AD in mild cognitive impairment (MCI) stage in order to improve treatment outcomes. 40 patients with MCI and AD, and 20 apparently healthy controls were investigated. Plasma levels of miRNA -483-5p were measured by real time polymerase chain reaction (PCR) and expressed as fold change. Receiver operating characteristic (ROC) curve analysis was done to assess diagnostic performance of the assay. Plasma levels of miRNA-483-5p were higher in MCI and AD patients than controls (mean = 8.04, 2.84 and 0.21 respectively, P<0.001), and decreased in AD patients in comparison to MCI patients (mean = 2.84 and 8.04 respectively, P = 0.032). There were significant positive correlations between plasma levels of miRNA-483-5p and age (r = 0.338, P= 0.008) and Dementia Rating (DR) scale (r = 0.351, P = 0.026), and significant negative correlations between plasma levels of miRNA-483-5p and Functional Daily Living Activity (FDLA) scale (r = -0.441, P<0.001), Mini Mental State Examination(MMSE) (r = -0.478, P< 0.001) and Montreal Cognitive Assessment (MOCA) scale (r = -0.396, P= 0.002). ROC curves revealed that miRNA-483-5p has high diagnostic performance in differentiating MCI and AD patients from healthy controls with specificity 95%, 90% and sensitivity 85%, 90% respectively. In conclusion, miRNA-483-5p may be a promising non -invasive biomarker for early diagnosis of AD in MCI stage.

摘要

阿尔茨海默病(AD)是一种不可逆转的、进行性的神经退行性疾病,占老年痴呆症病例的 62%。早期诊断 AD 对于成功治疗至关重要,以便减缓疾病进展并避免恶化。目前用于 AD 的诊断工具无法在早期检测到疾病;此外,它们仍然存在一些局限性。许多研究表明,microRNAs(miRNAs)与 AD 的发病机制有关,其在血液中的水平变化使它们成为 AD 的潜在生物标志物。我们旨在评估血浆 microRNA-483-5p 是否可作为轻度认知障碍(MCI)期 AD 的非侵入性生物标志物,以改善治疗效果。研究了 40 名 MCI 和 AD 患者以及 20 名明显健康的对照组。通过实时聚合酶链反应(PCR)测量血浆 miRNA-483-5p 水平,并表示为倍数变化。进行了接收者操作特征(ROC)曲线分析,以评估该测定的诊断性能。MCI 和 AD 患者的血浆 miRNA-483-5p 水平高于对照组(平均值分别为 8.04、2.84 和 0.21,P<0.001),AD 患者的血浆 miRNA-483-5p 水平低于 MCI 患者(平均值分别为 2.84 和 8.04,P=0.032)。血浆 miRNA-483-5p 水平与年龄(r=0.338,P=0.008)和痴呆症评定量表(DR)(r=0.351,P=0.026)呈显著正相关,与功能日常生活活动量表(FDLA)(r=-0.441,P<0.001)、简易精神状态检查表(MMSE)(r=-0.478,P<0.001)和蒙特利尔认知评估量表(MOCA)(r=-0.396,P=0.002)呈显著负相关。ROC 曲线显示,miRNA-483-5p 具有区分 MCI 和 AD 患者与健康对照组的高诊断性能,特异性分别为 95%、90%,敏感性分别为 85%、90%。总之,miRNA-483-5p 可能是 MCI 期 AD 早期诊断的一种有前途的非侵入性生物标志物。

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