精准医学杂志2026，Vol.41Issue(2)：146-151,6.DOI:10.13362/j.jpmed.202641036
脑脊液基质金属蛋白酶水平与阿尔茨海默病关系的研究
Association of the levels of matrix metalloproteinases in cerebrospinal fluid with Alzheimer's disease
摘要
Abstract
Objective To investigate the association of the levels of matrix metalloproteinases(MMPs)in cerebrospinal fluid(CSF)with the core pathological biomarkers of Alzheimer's disease(AD)and the cognitive function of AD.Methods A total of 497 subjects were selected from the Alzheimer's Disease Neuroimaging Initiative(ADNI)database,and related data were collected,including the levels of CSF MMPs(MMP-2,MMP-3,MMP-10,and MMP-9/TIMP-1 ratio),the core biomarkers for AD(Aβ42,phosphorylated tau[P-tau],and total tau[T-tau]),and cognitive function scores(MMSE,ADNI_MEM,ADNI_EF,ADNI_LAN,and ADNI_VS).The multiple linear regression analysis was used to assess whether the levels of CSF MMPs had a linear association with the core pathological biomarkers of AD and the cognitive function of AD.The linear mixed-effects model was used to evaluate the effect of the levels of CSF MMPs on cognitive decline.A mediation analysis was used to assess the media-ting effect of the core pathological biomarkers of AD in the association between CSF MMPs and cognitive function.Results The multiple linear regression analysis showed that CSF MMP-10,MMP-3,and MMP-9/TIMP-1 ratio were positively associated with the levels of CSF P-tau and T-tau(P＜0.05),while CSF MMP-10 was negatively associated with CSF Aβ42(P＜0.05),and the level of CSF MMP-10 was negatively associated with ADNI_MEM,ADNI_EF,ADNI_LAN,and ADNI_VS scores(P＜0.05).The linear mixed-effects model analysis showed that the high level of CSF MMP-10 was associated with the rapid reductions in cog-nitive function scores such as ADNI_MEM,ADNI_EF,ADNI_LAN,and ADNI_VS(P＜0.05).The mediation analysis showed that CSF Aβ42,P-tau,and T-tau mediated the association between CSF MMP-10 and cognitive function.Conclusion CSF MMP-10 level is significantly associated with the core pathological biomarkers of AD and cognitive decline in AD,and CSF MMP-10 may be involved in cognitive decline by affecting the core pathological biomarkers of AD.关键词
阿尔茨海默病/基质金属蛋白酶10/基质金属蛋白酶抑制剂/Tau蛋白质类/淀粉样β肽类/认知功能障碍/纵向研究/中介分析Key words
Alzheimer disease/Matrix metalloproteinase 10/Matrix metalloproteinase inhibitors/Tau proteins/Amy-loid beta-peptides/Cognitive dysfunction/Longitudinal studies/Mediation analysis分类
医药卫生引用本文复制引用
朱阳可,胡浩,谭兰..脑脊液基质金属蛋白酶水平与阿尔茨海默病关系的研究[J].精准医学杂志,2026,41(2):146-151,6.基金项目
中国科技创新2030-"脑科学与类脑研究"重大项目(2022ZD0211600) （2022ZD0211600）
