Fig. 2
From: Cholestenoic acid, an endogenous cholesterol metabolite, is a potent γ-secretase modulator
The effects of Cyp27a1 and Cyp7b1 genetic reductions on brain mAβ levels. a CA is found in the acidic cholesterol elimination pathway. Cholesterol is hydrolyzed by Cyp27a1 to produce 27-hydroxycholesterol (27-OHC) and CA sequentially. CA is further metabolized by Cyp7b1 generating CA derivatives, 7α-hydroxy-cholestenoic acid (7α-OH-CA) and 7α-hydroxy-4-oxo-cholestenoic acid (7α-OH-4-CA). Genetic deletion of Cyp27a1 is predicted to decrease endogenous CA levels, whereas the deletion of Cyp7b1 is predicted to accumulate CA. b Cyp27a1 (−/−) increased brain mAβ42/Aβ40 ratio compared to Cyp27a1 (+/+) by ~20 %. c-d Cyp7b1 (−/−) decreased the ratio between mAβ42 to mAβ40 by ~20 % compared to Cyp7b1 (+/+), whereas increased the ratio of mAβ38/Aβ40 by ~30 %. 6–8 mice were tested in the group. The results were analyzed by one-way analysis of variance (ANOVA) followed by Dunnett’s multiple comparisons. *p < 0.05