Objective To explore the correlation between plasma direct bilirubin (DBI) and the severity of Alzheimer′s disease (AD). Methods 110 patients with AD treated in our hospital from January 2019 to June 2021 were selected as AD group, and 60 healthy people who underwent routine physical examination in our hospital in the same period were selected as the control group. According to the score of MMSE, AD group was divided into mild dementia group (21~26 points, n=46), moderate dementia group (10~20 points, n=35)and severe dementia group(≤10 points, n=29).High sensitivity C-reactive protein (hs-CRP), DBI, a-lipoprotein(LP(a)), interleukin-17 (IL-17) and interleukin-6 (IL-6) were detected by enzyme-linked immunosorbent assay. The clinical factors affecting AD patients were analyzed by univariate analysis, and the main risk factors affecting AD patients were analyzed by logistic regression. The expression of MMSE score and DBI level in different AD severity and healthy population were compared, and the correlation between plasma DBI and MMSE score was analyzed. Results Compared with the control group, hs-CRP and IL-6 in AD group increased significantly, DBI and LP(a)decreased significantly (all P<0.05). Logistic regression model analysis showed that low DBI and LP(a)and high hs-CRP, IL-6 and Hcy were the risk factors for AD patients (P＜0.05). Compared with the control group, the MMSE score and DBI level in AD group were significantly lower(all P<0.05). There was a significant positive correlation between plasma DBI level and MMSE score in patients with AD(P<0.05). The AUC of the area under the ROC curve of plasma DBI in AD was 0.831. The specificity was 73.25%, the sensitivity was 77.50%, and the cut-off value was 2.56μmol/L.Conclusion The decrease of plasma DBI level in AD patients is a risk factor for the onset of AD patients, which is related to the severity of AD patients. The detection of plasma DBI level has high diagnostic value for AD, or can be used as an indicator for the diagnosis and disease evaluation of AD