Effects of folic acid on Aβ deposition and BACE1 expression in brain of APP/PS1 transgenic mouse

  Objective   To explore the effect and mechanisms of folic acid on deposition of amyloid β-protein (Aβ) in brain tissues of mice with Alzheimer’s disease.

  Methods   Forty 6-month-old male APP/PS1 mice were randomly assigned into four groups: a folate deficiency group (AD + FA-D) with folic acid deficient feed and daily gavage of water, a folate control group (AD + FA-N) with normal feed and daily gavage with water, and low- and high-dose folate groups (AD + FA-L and AD + FA-H) with normal feed and daily gavage of 120 and 600 μg/kg folic acid; ten 6-month-old male wild type mice with normal feed and daily gavage of water (WT + FA-N) were used as negative controls. The treatments were performed consecutively for 60 days. By the end of the treatments, the mRNA expression of β-site amyloid precursor protein cleaving enzyme-1 (BACE1) in brain tissues was quantified by real-time PCR. The protein expression level of β-site amyloid precursor protein cleaving enzyme-1 (BACE1) in brain tissues was detected with Western blot; the expression of Aβ in brain tissues was measured with immunohistochemistry; the expression levels of Aβ_1–40 and Aβ_1–42 in brain tissues were measured with enzyme-linked immunosorbent assay (ELISA).

  Results   The expression of Aβ decreased in AD+FA-H group and increased in AD+FA-D group significantly compared to that in AD+FA-N group (P < 0.05); the content of Aβ_1–42 (0.209 ± 0.041) decreased in AD + FA-H group and increased (0.396 ± 0.043) in AD + FA-D group significantly compared to that (0.295 ± 0.034) in AD + FA-N group (P < 0.05); the expression of BACE1 mRNA increased in AD + FA-D group (21.97 ± 4.396) but decreased in AD + FA-L and AD + FA-H groups (9.932 ± 1.903 and 10.53 ± 2.750) significantly compared to that (15.99 ± 1.434) in AD + FA-N group (P < 0.05 for all); the expression of BACE1 protein increased in AD + FA-D group (1.655 ± 0.241) but decreased in AD + FA-L and AD + FA-H groups (1.003 ± 0.271 and 0.906 ± 0.188) significantly compared to that (1.371 ± 0.213) in AD + FA-N group (P < 0.05 for all).

  Conclusion   The study results show that folic acid supplementation can reduce brain Aβ deposition and Aβ_1–42 content and the mechanism of the effects may be related to folic acid-induced inhibition of BACE1 expression associated with Aβ formation in brain tissue of mice.