Kwok Kei Mak, Karin JeeEun Nam, Yi-Fang Chuang, Liang-Kung Chen
{"title":"基质金属蛋白酶和金属蛋白酶组织抑制剂作为阿尔茨海默病的生物标志物：一项荟萃分析","authors":"Kwok Kei Mak, Karin JeeEun Nam, Yi-Fang Chuang, Liang-Kung Chen","doi":"10.1016/j.brainres.2025.149954","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>This study systematically investigated the associations of levels of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) with clinical-phase Alzheimer's disease (AD) to evaluate their potential as biomarkers.</p><p><strong>Methods: </strong>A systematic search of major English and Asian language databases was conducted from inception to December 2024. Following the screening process using predefined inclusion and exclusion criteria, 12 human studies were selected for review. The sample consisted of 1316 participants (806 with clinical-phase AD patients and 510 controls), including 49.7% males with a mean age of 71.2. The outcomes for comparisons between AD status groups were concentrations of gelatinases (MMP-2 and MMP-9) and stromelysins (MMP-3, MMP-10), TIMPs (TIMP-1 and TIMP-2), as well as the MMP-9/TIMP-1 ratio in body fluids. Pooled standardized mean differences (SMDs) were computed using random-effects models and adjusting for the moderators, comprising demographic factors (population, sex, age) and body fluid type, in the meta-analysis. Forest plots and funnel plots were generated to visualize the results and assess publication biases, respectively.</p><p><strong>Results: </strong>Levels of MMP-3 and MMP-9 were significantly higher in AD patients than in controls with the corresponding pooled SMDs (95 %CI) of 0.69 (0.25 to 1.13) and 0.45 (0.08 to 0.82). The association of MMP-3 level with AD status was moderated by population, sex, and body fluid type, whereas the association of MMP-9 was not. The Egger's tests revealed no statistically significant publication biases (P > 0.05).</p><p><strong>Discussion: </strong>This study provides a summary of the past-decade findings about the levels of MMPs and TIMPs in AD patients and controls. Our findings indicate that elevated MMP-3 and MMP-9 are associated with AD. MMP-9, regardless of body fluid type, could be universally used for screening AD individuals with relevance across various demographic groups.</p>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":" ","pages":"149954"},"PeriodicalIF":2.6000,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Matrix metalloproteinases and tissue inhibitors of metalloproteinases as the biomarkers of Alzheimer's disease: a meta-analysis.\",\"authors\":\"Kwok Kei Mak, Karin JeeEun Nam, Yi-Fang Chuang, Liang-Kung Chen\",\"doi\":\"10.1016/j.brainres.2025.149954\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>This study systematically investigated the associations of levels of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) with clinical-phase Alzheimer's disease (AD) to evaluate their potential as biomarkers.</p><p><strong>Methods: </strong>A systematic search of major English and Asian language databases was conducted from inception to December 2024. Following the screening process using predefined inclusion and exclusion criteria, 12 human studies were selected for review. The sample consisted of 1316 participants (806 with clinical-phase AD patients and 510 controls), including 49.7% males with a mean age of 71.2. The outcomes for comparisons between AD status groups were concentrations of gelatinases (MMP-2 and MMP-9) and stromelysins (MMP-3, MMP-10), TIMPs (TIMP-1 and TIMP-2), as well as the MMP-9/TIMP-1 ratio in body fluids. Pooled standardized mean differences (SMDs) were computed using random-effects models and adjusting for the moderators, comprising demographic factors (population, sex, age) and body fluid type, in the meta-analysis. Forest plots and funnel plots were generated to visualize the results and assess publication biases, respectively.</p><p><strong>Results: </strong>Levels of MMP-3 and MMP-9 were significantly higher in AD patients than in controls with the corresponding pooled SMDs (95 %CI) of 0.69 (0.25 to 1.13) and 0.45 (0.08 to 0.82). The association of MMP-3 level with AD status was moderated by population, sex, and body fluid type, whereas the association of MMP-9 was not. The Egger's tests revealed no statistically significant publication biases (P > 0.05).</p><p><strong>Discussion: </strong>This study provides a summary of the past-decade findings about the levels of MMPs and TIMPs in AD patients and controls. Our findings indicate that elevated MMP-3 and MMP-9 are associated with AD. MMP-9, regardless of body fluid type, could be universally used for screening AD individuals with relevance across various demographic groups.</p>\",\"PeriodicalId\":9083,\"journal\":{\"name\":\"Brain Research\",\"volume\":\" \",\"pages\":\"149954\"},\"PeriodicalIF\":2.6000,\"publicationDate\":\"2025-09-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Brain Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.brainres.2025.149954\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Brain Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.brainres.2025.149954","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
Matrix metalloproteinases and tissue inhibitors of metalloproteinases as the biomarkers of Alzheimer's disease: a meta-analysis.
Introduction: This study systematically investigated the associations of levels of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) with clinical-phase Alzheimer's disease (AD) to evaluate their potential as biomarkers.
Methods: A systematic search of major English and Asian language databases was conducted from inception to December 2024. Following the screening process using predefined inclusion and exclusion criteria, 12 human studies were selected for review. The sample consisted of 1316 participants (806 with clinical-phase AD patients and 510 controls), including 49.7% males with a mean age of 71.2. The outcomes for comparisons between AD status groups were concentrations of gelatinases (MMP-2 and MMP-9) and stromelysins (MMP-3, MMP-10), TIMPs (TIMP-1 and TIMP-2), as well as the MMP-9/TIMP-1 ratio in body fluids. Pooled standardized mean differences (SMDs) were computed using random-effects models and adjusting for the moderators, comprising demographic factors (population, sex, age) and body fluid type, in the meta-analysis. Forest plots and funnel plots were generated to visualize the results and assess publication biases, respectively.
Results: Levels of MMP-3 and MMP-9 were significantly higher in AD patients than in controls with the corresponding pooled SMDs (95 %CI) of 0.69 (0.25 to 1.13) and 0.45 (0.08 to 0.82). The association of MMP-3 level with AD status was moderated by population, sex, and body fluid type, whereas the association of MMP-9 was not. The Egger's tests revealed no statistically significant publication biases (P > 0.05).
Discussion: This study provides a summary of the past-decade findings about the levels of MMPs and TIMPs in AD patients and controls. Our findings indicate that elevated MMP-3 and MMP-9 are associated with AD. MMP-9, regardless of body fluid type, could be universally used for screening AD individuals with relevance across various demographic groups.
期刊介绍：
An international multidisciplinary journal devoted to fundamental research in the brain sciences.
Brain Research publishes papers reporting interdisciplinary investigations of nervous system structure and function that are of general interest to the international community of neuroscientists. As is evident from the journals name, its scope is broad, ranging from cellular and molecular studies through systems neuroscience, cognition and disease. Invited reviews are also published; suggestions for and inquiries about potential reviews are welcomed.
With the appearance of the final issue of the 2011 subscription, Vol. 67/1-2 (24 June 2011), Brain Research Reviews has ceased publication as a distinct journal separate from Brain Research. Review articles accepted for Brain Research are now published in that journal.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
