神经炎症、血管风险和阿尔茨海默病生物标志物之间的相关性分析

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[中图分类号] R745.7 [文献标志码］ A

Association between neuroinflammation， vascular risk， and biomarkers in Alzheimer’s disease CHEN Yanming，HU Heying，CUI Ruiping，HU Hao，TAN Chenchen，TAN Lan （Qingdao Medical College of Qingdao University，Qingdao 266071，China）

[ABSTRACT]ObjectiveTo investigate the asociation between neuroinflammation，vascular risk，and biomarkers in Alzheimer’sdisease（AD）.MethodsAtotalof1O79individualswithoutADwereselectedassubjectsfromtheChinaAlzheimer's Biomarkerand Lifestyle studycohort，andFramingham General CardiovascularRisk Score（FGCRS）was used toassessthe vascularriskofthe subjects.Themultiplelinearregressionmodelwasusedtoinvestigate thecorelationofFGCRS withADbio markers in cerebrospinal fluid（CSF） （ β- amyloid 42 [Aβ42] ， β⋅ amyloid 40[Aβ40] ，phosphorylated tau[P-tau]，total tau[T-tau]， Aβ42/Aβ40 ratio，T-tau/ Aβ42 ratio，and P-tau/Aβ42 ratio]，neuroinflammatory factors in CSF（soluble triggering receptor expressednmyeloidcels 2[sTREM2]and progranulin[PGRN]），andperipheralblood inflammatorycells（whitebloodcelcount [WBC]，neutrophil count[NEU]，lymphocyte count[LY]，monocyte count[MONO]，and neutrophil-to-lymphocyteratio [NLR]）.Mediation models wereconstructed with sTREM2 and PGRNas mediators toinvestigate the mediating efect of neuroinflammatory factors between vascular risk and ADbiomarkers.ResultsFGCRS was positivelycorelated withthe levels of Aβ42 ， Aβ40 ，P-tau，and T-tau in CSF ， and it was also positively correlated with the levels of sTREM2 and PGRN in CSF and the levels of WBC，NEU，NLR，and MONO in peripheral blood （β=0.120-0.228，t=3.285- （20 5.705，P<0.05 .PGRN and sTREM2 mediated the association between FGCRS and AD biomarkers in CSF （ A{β40 ，P-tau，T-tau， and Aβ42 ），with a mediation ratio of 26.75%-81.82% for sTREM2 and 9.66%-31.03% for PGRN. ConclusionThe increase in vascular riskmayinfluence thelevelsofADbiomarkers inCSFbyincreasing thelevelsof neuroinflammatoryfactors in CSF， thereby promoting the development and progression of AD.

[KEY WORDs]Alzheimer disease；Inflammation；Risk factors；Vascular risk；Amyloid;Progranulins；Bloodcellcount; Cerebrospinal fluid; Soluble triggering receptor expressed on myeloid cells 2； Biomarkers

阿尔茨海默病（Alzheimer'sdisease，AD）是一种神经退行性疾病，其突出的病理改变是 β -淀粉样蛋白（Aβ）在神经细胞外沉积形成神经炎性斑块和过度磷酸化的tau蛋白在神经细胞内聚集形成的神经原纤维缠结[1]。（剩余10249字）