脑脊液基质金属蛋白酶水平与阿尔茨海默病关系的研究OA

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.