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神经营养因子及其受体作为阿尔茨海默病有希望的血液生物标志物:一项基因表达分析研究。

Neurotrophin growth factors and their receptors as promising blood biomarkers for Alzheimer's Disease: a gene expression analysis study.

机构信息

Clinical Research Development Unit of Tabriz Valiasr Hospital, Tabriz University of Medical Sciences, Tabriz, Iran.

Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.

出版信息

Mol Biol Rep. 2024 Jan 2;51(1):49. doi: 10.1007/s11033-023-08959-4.

Abstract

BACKGROUND

Alzheimer's disease (AD) is a multifaceted neurological ailment affecting more than 50 million individuals globally, distinguished by a deterioration in memory and cognitive abilities. Investigating neurotrophin growth factors could offer significant contributions to understanding AD progression and prospective therapeutic interventions.

METHODS AND RESULTS

The present investigation collected blood samples from 50 patients diagnosed with AD and 50 healthy individuals serving as controls. The mRNA expression levels of neurotrophin growth factors and their receptors were measured using quantitative PCR. A Bayesian regression model was used in the research to assess the relationship between gene expression levels and demographic characteristics such as age and gender. The correlations between variables were analyzed using Spearman correlation coefficients, and the diagnostic potential was assessed using a Receiver Operating Characteristic curve. NTRK2, TrkA, TrkC, and BDNF expression levels were found to be considerably lower (p-value < 0.05) in the blood samples of AD patients compared to the control group. The expression of BDNF exhibited the most substantial decrease in comparison to other neurotrophin growth factors. Correlation analysis indicates a statistically significant positive association between the genes. The ROC analysis showed that BDNF exhibited the greatest Area Under the Curve (AUC) value of 0.76, accompanied by a sensitivity of 70% and specificity of 66%. TrkC, TrkA, and NTRK2 demonstrated considerable diagnostic potential in distinguishing between cases and controls.

CONCLUSION

The observed decrease in the expression levels of NTRK2, TrkA, TrkC, and BDNF in AD patients, along with the identified associations between specific genes and their diagnostic capacity, indicate that these expressions have the potential to function as biomarkers for the diagnosis and treatment of AD.

摘要

背景

阿尔茨海默病(AD)是一种多方面的神经疾病,影响着全球超过 5000 万人,其特征是记忆力和认知能力的恶化。研究神经生长因子可能对了解 AD 的进展和潜在的治疗干预有重要贡献。

方法和结果

本研究从 50 名 AD 患者和 50 名健康对照者中采集了血液样本。使用定量 PCR 测量了神经生长因子及其受体的 mRNA 表达水平。研究中使用贝叶斯回归模型评估了基因表达水平与年龄和性别等人口统计学特征之间的关系。使用 Spearman 相关系数分析了变量之间的相关性,并使用接受者操作特征曲线评估了诊断潜力。与对照组相比,AD 患者的血液样本中 NTRK2、TrkA、TrkC 和 BDNF 的表达水平明显较低(p 值<0.05)。与其他神经生长因子相比,BDNF 的表达下降最为显著。相关性分析表明基因之间存在显著的正相关。ROC 分析显示 BDNF 表现出最大的 AUC 值为 0.76,灵敏度为 70%,特异性为 66%。TrkC、TrkA 和 NTRK2 在区分病例和对照组方面具有相当大的诊断潜力。

结论

AD 患者中 NTRK2、TrkA、TrkC 和 BDNF 的表达水平下降,以及特定基因之间的关联及其诊断能力,表明这些表达可能作为 AD 的诊断和治疗的生物标志物。

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