Abstract: Objective To explore the clinical value of plasma and cerebrospinal fluid Dynamic-related protein 1(Drp1) as biomarkers in the early diagnosis of Alzheimer's disease. Methods Total 125 patients in the department of geriatrics of Hangzhou 7th people's hospital from June 2015 to June 2017 were selected as subjects, including 67 cases of mild cognitive impairment(MCI), 58 cases of AD, and 32 normal control as control. The cognitive function score were assayed according to Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) and Activity of Daily Living Scale (ADL). The levels of Drp1 and SNO-Drp1 in plasma and cerebrospinal fluid were tested by using Western blot. Results There was significant difference in MMSE and MoCA scores among the three groups (P<0.05). The plasma Drp1 of AD group was significantly lower than that of the control group (P<0.05). The expression of SNO-Drp1 in cerebrospinal fluid in AD group was significantly higher than those in the MCI group and control group (P<0.05), and the SNO-Drp1/Drp1 ratio in AD group was significantly higher than that in the control group. The sensitivity and specificity by ROC curve for MCI were 77.6% and 56.2%, and for AD were 86.2% and 87.5%. Conclusion The sensitivity and specificity of cerebrospinal fluid SNO-Drp1/Drp1 ratio for AD diagnosis is high and proximate, which is worthy of promotion.