A confirmatory study on potential plasma protein markers for Alzheimer's disease
Objective To investigate the plasma differential protein expressions between patients with Alzheimer's disease(AD)and normal controls,and to search plasma protein markers or protein combi-nations with screening or diagnostic significance.Methods Plasma samples from 98 patients with dementia of Alzheimer type(DAT),102 patients with mild cognitive impairment(MCI)and 101 normal controls(NC)were collected from Wuxi Mental Health Center and Shanghai Mental Health Center from 2016 to 2018.The expression levels of 50 kinds of plasma proteins in all plasma samples were detected by Milliplex MAP assays(xMAP).Analysis of variance,regression analysis,discriminant analysis,and ROC analysis on the data were performed using SPSS 20.0 software.Results(1)Compared with the NC group,26 plasma proteins were up-regulated and 4 proteins were down-regulated in DAT group,while 6 proteins were up-regu-lated and 4 proteins were down-regulated in MCI group(all P＜0.05).Compared with the NC group,6 pro-teins were upregulated in both MIC group and DAT group,which were clusterin(Clust)(613.41(278.89),761.76(358.60),473.01(321.73)),cystatin C(Cys C)(691.88(441.34),852.28(551.75),548.64(545.28)),transthyretin(TTR)(207.10(168.60),220.95(151.20),152.89(162.70)),complement factor H(Com FH)(331.67(218.37),361.69(124.64),225.79(236.82)),soluble intercellular adhe-sion molecule-1(sICAM1)(109.30(49.47),137.21(50.36),87.06(57.59),and apolipoprotein E(APOE)(79.33(78.13),79.31(68.85),54.88(67.34)).The serum amyloid P component(SAP)was downregulated in both DAT and MCI groups(121.23(311.31),92.39(156.62),125.00(242.82))com-pared with NC group.(2)Three sets of protein combination were screened by differential analysis,regression analysis,and discriminant analysis,including 8 proteins,9 proteins and 7 proteins,respectively.And SAP,an-giotensin(AGT),osteopontin(OPN),and complement C4(Com C4)were the compared with NC group most frequently selected protein.The screening correct rate of three protein combinations were respectively 67.4％-71.4％for AD,82.4％-88.4％for DAT,and 60.6％-63.5％for MCI.Conclusions A variety of plasma proteins such as Clust,Cys C,TTR,Com FH,sICAMl,APOE are upregulated,while SAP is downregulated in AD patients.These differential protein combinations can help with early diagnosis of dementia with Alzheimer type.SAP,AGT,OPN and Com C4 may be potential markers for early screening or diagnosis of AD.
Alzheimer's diseaseMild cognitive impairmentEarly diagnosisPlasma protein markers
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