Objective To explore the expression levels of SPARC related modular calcium binding 1(SMOC1)and olfactomedin-3(OLFM3)in the cerebrospinal fluid of Alzheimer's disease(AD)patients and their value in evaluating the severity of the disease.Methods A total of 108 AD patients(AD group)treated at Baoji People's Hospital from January 2020 to January 2023 were selected,and 60 non cognitive dysfunction patients who underwent lumbar puncture examination during the same period were selected as the control group.Enzyme-linked immunosorbent assay(ELISA)was used to detect cerebrospinal fluid SMOC1,OLFML3,β-Amyloid protein(Aβ1-40,Aβ1-42)and P-Tau protein levels.Pearson correlation analysis was conducted to analyze cerebrospinal fluid SMOC1,and OLFML3 levels and their correlation with clinical indicators.Logistic regression was used to analyze the influencing factors of AD severity.Receiver operating characteristic curves were used to analyze the predictive value of cerebrospinal fluid SMOC1 and OLFML3 on the severity of Alzheimer's disease.Results The levels of SMOC1(68.47±11.23 ng/L),OLFML3(110.58±21.39 ng/L),P-Tau(569.07±97.24 ng/L)and CDR score(1.5 score)in the cerebrospinal fluid of the AD group were higher than those in the control group(22.60±4.16 ng/L,36.94±6.97ng/L,182.66±55.37,0 score),while Aβ1-42(292.23±55.36 ng/L),MoCA score(7.88±2.05 score)and MMSE score(13.15±2.39 score)were lower than those in the control group(397.16±60.57ng/L,23.13±4.31 score,28.02±4.26 score),and the differences were statistically significant(t=30.465,25.885,28.313,51.211,11.380,31.038,29.013,all P＜0.05).SMOC1 and OLFML3 of the cerebrospinal fluid in the AD group were positively correlated with P-Tau and CDR score(r=0.703,0.634;0.682,0.713,all P＜0.05),but were negatively correlated with Aβ1-42,MoCA score and MMSE score(r=-0.662,-0.599;-0.660,-0.588;-0.745,-0.731,all P＜0.05).SMOC1(89.90±12.17 ng/L),OLFML3(142.46±22.48),and P-Tau(618.83±98.19 ng/L)in the cerebrospinal fluid of AD patients in the moderate to severe group were higher than those in the mild group(56.36±10.52 ng/L,92.56±20.25 ng/L,542.25±95.30 ng/L),Aβ1-42 in the moderate to severe group(260.76±53.60 ng/L)was lower than those in the mild group(310.02±56.54 ng/L),and the differences were statistically significant(t=15.029,11.818,3.968,4.430,all P<0.05).SMOC1(OR=1.451,95%CI:1.120～1.879),OLFML3(OR=1.442,95%CI:1.096～1.897)and P-Tau(OR=1.589,95%CI:1.258～2.006)in cerebrospinal fluid were risk factors for moderate to severe cognitive impairment in AD patients,while Aβ1-42 was a protective factor.The AUC(95%CI)of SMOC1,OLFML3 in cerebrospinal fluid,and their combinative forecasting evaluating moderate to severe AD patients were 0.882(0.844～0.929),0.846(0.805～0.877)and 0.931(0.883～0.965),respectively,and their combinative forecasting was higher than two individual indicators(Z=3.558,4.172,P=0.004,0.000).Conclusion The levels of SMOC1 and OLFML3 in cerebrospinal fluid are elevated in AD patients,which are related to the severity of AD.The combinative forecasting of the two has high predictive value for moderate to severe AD.