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Background: Alzheimer's disease (AD) has high a prevalence rate, high medical costs, and care difficulties, and has become a serious social and economic problem in our aging society. So far, there has not been a reliable and objective diagnostic criteria for AD found. In recent years, there have been many domestic and foreign studies on the biological markers of cerebrospinal fluid in the patients with AD, and high levels of the T-tau, P-tau found in cerebrospinal fluid (CSF) is at this point an indisputable fact. However, the relationship between these markers and the severity of dementia, as well as the development of the disease, should be further studied. Objective: Compare the CSF level of total tau (T-tau) and phosphorylated tau at threonine 231 ( P-tau231 ) between patients with moderate to severe Alzheimer's disease (AD) and those with vascular dementia (VD) at baseline, and 6 month follow-up. Observe the differences between patients with AD and control group, as well as the changes as the disease develops. Methods: There were 11 patients with moderate AD (10 ≤ MMSE ≤ 20), 10 patients with severe AD (MMSE ≤ 9), and 7 age-matched patients with severe VD at baseline, among which 7 AD patients and 6 VD patients completed the 6 months follow-up. CSF levels of T-tau, P-tau231 were measured with sandwich ELISA. Result: At baseline, the concentrations of the CSF level of T-tau were 470.08 (263.58) pg/mL in the AD group and 208.76 (42.24) pg/mL in the VD group. This difference was statistically significant (Z= -3.369, p <0.001). The concentrations of CSF level of P-tau231 were 90.94 (49.86) pg/mL in the AD group and 42.96 (13.10) pg/ mL in the VD group. This difference was also statistically significant (Z = -3.237, p <0.001). Compared to patients with severe VD, the concentration of CSF T-tau in patients with severe AD was significantly higher (Z= -2.830, p = 0.005), as well as the concentration of CSF P-tau231 (Z = -2.392, p = 0.017). The concentration of CSF P-tau231 in the patients with moderate AD was significantly higher than that in the patients with severe VD (Z = -2.605, p = 0.009). At the 6 months follow-up, there were no statistically significant differences in the changes of CSF T-tau and CSF P-tau231 concentrations between the AD group and VD group. Conclusion: The CSF level of T-tau and P-tau231 in the AD patients was significantly higher than that in the VD patients. The concentration of CSF P-tau231 in the moderate AD patients was significantly higher than that in the patients with severe AD. During the 6 months follow-up, the changes of the CSF concentrations of T-tau and P-tau231 between AD group and VD group were not statistically significant. [ABSTRACT FROM AUTHOR]