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基质重塑酶作为阿尔茨海默病神经退行性变潜在的体液生物标志物。

Matrix Remodeling Enzymes as Potential Fluid Biomarkers of Neurodegeneration in Alzheimer's Disease.

机构信息

Department of Biochemistry, Faculty of Medicine, University of Niš, 18000 Niš, Serbia.

Faculty of Medicine, University of Niš, 18000 Niš, Serbia.

出版信息

Int J Mol Sci. 2024 May 24;25(11):5703. doi: 10.3390/ijms25115703.

Abstract

This study investigated the diagnostic accuracy of plasma biomarkers-specifically, matrix metalloproteinase (MMP-9), tissue inhibitor of metalloproteinase (TIMP-1), CD147, and the MMP-/TIMP-1 ratio in patients with Alzheimer's disease (AD) dementia. The research cohort comprised patients diagnosed with probable AD dementia and a control group of cognitively unimpaired (CU) individuals. Neuroradiological assessments included brain magnetic resonance imaging (MRI) following dementia protocols, with subsequent volumetric analysis. Additionally, cerebrospinal fluid (CSF) AD biomarkers were classified using the A/T/N system, and apolipoprotein E () ε4 carrier status was determined. Findings revealed elevated plasma levels of MMP-9 and TIMP-1 in AD dementia patients compared to CU individuals. Receiver operating characteristic (ROC) curve analysis demonstrated significant differences in the areas under the curve (AUC) for MMP-9 ( < 0.001) and TIMP-1 ( < 0.001). Notably, plasma TIMP-1 levels were significantly lower in ε4+ patients than in ε4- patients ( = 0.041). Furthermore, ε4+ patients exhibited reduced hippocampal volume, particularly in total, right, and left hippocampal measurements. TIMP-1 levels exhibited a positive correlation, while the MMP-9/TIMP-1 ratio showed a negative correlation with hippocampal volume parameters. This study sheds light on the potential use of TIMP-1 as a diagnostic marker and its association with hippocampal changes in AD.

摘要

本研究旨在探讨血浆生物标志物(具体为基质金属蛋白酶-9 [MMP-9]、金属蛋白酶组织抑制剂-1 [TIMP-1]、CD147 以及 MMP/TIMP-1 比值)在阿尔茨海默病(AD)痴呆患者中的诊断准确性。研究队列包括经诊断患有可能 AD 痴呆的患者和认知正常(CU)的对照组。神经影像学评估包括遵循痴呆协议的脑部磁共振成像(MRI),随后进行容积分析。此外,还采用 A/T/N 系统对脑脊液(CSF)AD 生物标志物进行分类,并确定载脂蛋白 E ( ) ε4 携带状态。研究结果显示,AD 痴呆患者的血浆 MMP-9 和 TIMP-1 水平高于 CU 个体。受试者工作特征(ROC)曲线分析显示,MMP-9( < 0.001)和 TIMP-1( < 0.001)的曲线下面积(AUC)存在显著差异。值得注意的是,ε4+患者的血浆 TIMP-1 水平显著低于 ε4-患者( = 0.041)。此外,ε4+患者的海马体积减小,尤其是在总海马、右侧海马和左侧海马的测量中。TIMP-1 水平呈正相关,而 MMP-9/TIMP-1 比值与海马体积参数呈负相关。本研究揭示了 TIMP-1 作为诊断标志物的潜在用途及其与 AD 中海马变化的关联。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1236/11171655/905b534d3946/ijms-25-05703-g001.jpg

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