Objective To observe the effects of folic acid ( FA) supplementation on the expression of Flotillin-1 and β-amyloid protein ( Aβ) -metabolism-related proteins in the brains of inflammation-stimulated Alzheimer’ s disease (AD) mice. Methods Twenty-seven 6-month-old male APP / PS1 mice were randomly divided into AD, AD+LPS, and AD+LPS+FA groups, with nine mice in each group. Nine C57BL / 6J male mice born within the same month were used as the Control group. The AD + LPS + FA group was given folic-acid-supplemented feed ( 8 mg / kg ) for 3 months of intervention, while the other three groups were fed normal feed. Lipopolysaccharide solution ( LPS, 250 μg / ( kg·d) ) was injected intraperitoneally into mice in the AD+LPS and AD+LPS+FA groups 1 week before the end of the experiment, and saline was injected into the remaining two groups. The serum inflammatory factors TNF-α and IL-6 levels and brain tissue Aβ1- 40 and Aβ1- 42 levels of mice in each group were detected by ELISA. Flotillin-1 protein expression in brain tissue was detected using Western blot, and the co-expression of Flotillin-1 and Aβ1- 42 / APP / PS1 / BACE1 in the cortical region of the brain was detected via immunofluorescence double-labeling. Results After ANOVA analysis, we found mice in the AD group had elevated serum TNF-α and IL-6 levels ( P<0. 05) , elevated levels of Aβ1- 40 and Aβ1- 42 ( P<0. 05) , increased expression of Flotillin-1 protein (P<0. 05) , and increased co-expression of Flotillin-1 and Aβ1- 42 / APP / PS1 / BACE1 in the cortical brain tissue (P<0. 05) compared with the Control group. Compared with mice in the AD group, those in the AD+LPS group had further increases in serum inflammatory factors and Aβ levels in the brain ( P<0. 05) and increased coexpression of Flotillin-1 and Aβ1- 42/ APP / BACE1 double-labeled proteins in their cortical brain tissue ( P<0. 05 ) .Compared with mice in the AD+LPS group, those in the AD+LPS+FA group had lower in vivo inflammation levels and Aβcontent in the brain ( P<0. 05) , lower brain tissue Flotillin-1 protein expression ( P<0. 05) , and lower Flotillin-1 and Aβ1- 42 / APP / PS1 / BACE1 protein co-expression in cortical brain tissue ( P<0. 05 ) . Conclusions Folic acid supplementation may reduce Flotillin-1 protein expression and Aβ deposition in the brain of AD inflammatory mice.