〔Abstract〕 Objective To investigate the correlation between the methylenetetrahydrofolate reductase(MTHFR)C677Tpolymorphism and disease in the course of Alzheimer′s disease(AD),as well as whether whether it is affected byAPOEgene. Methods A total of 74 AD patients, 85 aMCI patients and 81 healthy controls(HC) were included. The levels of serum homocysteine(Hcy), folate, and vitamin B12, as well as the genotypes ofMTHFR C677TandAPOE, were determined. Logistic regression analysis was conducted to explore the relationship betweenMTHFR C677Tpolymorphism and the risk of AD and aMCI, as well as in different APOE ε4 subgroups. Results Compared with HC group, the serum Hcy levels in AD group and aMCI group were significantly higher(P<0.001,P<0.001), while serum folate levels in aMCI group was significantly lower(P=0.017). The serum folate level was significantly lower(P=0.038) in individuals with theMTHFR TTgenotype compared to those withCCandCTgenotypes, while the serum Hcy level was significantly higher(P=0.002). Regression analysis showed that theMTHFR TTgenotype might increase the risk of aMCI in the subgroup ofAPOE ε4non-carriers(OR=3.670, 95%CI=1.077-12.509,P=0.038), but not inAPOE ε4carriers. Conclusion MTHFR C677Tpolymorphism plays an important role in Hcy metabolism, which leads to increased serum Hcy levels and decreased folate levels. InAPOE ε4non-carriers, theMTHFR TTgenotype may increase the risk of aMCI.