Systematic review of amyloid-beta clearance proteins from the brain to the periphery:implications for Alzheimer's disease diagnosis and therapeutic targets  

作　　者：Letian Huang Mingyue Liu Ze Li Bing Li Jiahe Wang Ke Zhang 

机构地区：[1]Department of Oncology,Shengjing Hospital of China Medical University,Shenyang,Liaoning Province,China [2]Department of Developmental Cell Biology,Key Laboratory of Cell Biology,Ministry of Public Health,China Medical University,Shenyang,Liaoning Province,China [3]Department of Family Medicine,Shengjing Hospital of China Medical University,Shenyang,Liaoning Province,China

出　　处：《Neural Regeneration Research》2025年第12期3574-3590,共17页中国神经再生研究(英文版)

基　　金：supported by the National Natural Science Foundation of China,No.81571046(to KZ);Key Project of Educational Department of Liaoning Province,No.LJKZ0755(to KZ);Project of Department of Science&Technology of Liaoning Province,No.2023JH2/20200116(to KZ);Shenyang Young and Middleaged Innovative Talents Support Program,No.RC210240(to KZ);the 345 Talent Project of Shengjing Hospital of China Medical University(to LH)。

摘　　要：Amyloid-beta clearance plays a key role in the pathogenesis of Alzheimer's disease.H oweve r,the variation in functional proteins involved in amyloid-beta clearance and their correlation with amyloid-beta levels remain unclea r.In this study,we conducted meta-analyses and a systematic review using studies from the PubMed,Embase,Web of Science,and Cochrane Library databases,including journal articles published from inception to J une 30,2023.The inclusion criteria included studies comparing the levels of functional proteins associated with amyloid-beta clearance in the blood,cere b rospinal fluid,and brain of healthy controls,patients with mild cognitive impairment,and patients with Alzheimer's disease.Additionally,we analyzed the correlation between these functional proteins and amyloid-beta levels in patients with Alzheimer's disease.The methodological quality of the studies was assessed via the Newcastle-Ottawa Scale.Owing to heterogeneity,we utilized either a fixed-effect or random-effect model to assess the 95%confidence interval(CI)of the standard mean difference(SMD)among healthy controls,patients with mild cognitive impairment,and patients with Alzheimer's disease.The findings revealed significant alterations in the levels of insulin-degrading enzymes,neprilysin,matrix metalloproteinase-9,cathepsin D,receptor for advanced glycation end products,and P-glycoprotein in the brains of patients with Alzheimer's disease,patients with mild cognitive impairment,and healthy controls.In cerebrospinal fluid,the levels of triggering receptor expressed on myeloid cells 2 and ubiquitin C-terminal hydrolase L1 are altered,whereas the levels of TREM2,CD40,CD40L,CD14,CD22,cathepsin D,cystatin C,andα2 M in peripheral blood differ.Notably,TREM2 and cathepsin D showed changes in both brain(SMD=0.31,95%CI:0.16-0.47,P<0.001,I^(2)=78.4%;SMD=1.24,95%CI:0.01-2.48,P=0.048,I^(2)=90.1%)and peripheral blood(SMD=1.01,95%CI:0.35-1.66,P=0.003,I^(2)=96.5%;SMD=7.55,95%CI:3.92-11.18,P<0.001,I^(2)=98.2%)samples.Furthermore,correlations were

关 键 词：Alzheimer’s disease amyloid-β blood‒brain barrier cerebrospinal fluid diagnostic biomarker meta-analysis mild cognitive impairment peripheral blood systematic review therapeutic targets 

分 类 号：R749.16[医药卫生—神经病学与精神病学]