Neuritic plaques are one of the major pathological hallmarks of Alzheimer's disease. They are formed by the aggregation of extracellular amyloid-β protein (Aβ), which is derived from the sequential cleavage of amyloid-β precursor protein (APP) by β- and γ-secretase. BACE1 is the main β-secretase in the pathogenic process of Alzheimer's disease, which is believed to be a rate-limiting step of Aβ production. Presenilin 1 (PS1) is the active center of the γ-secretase that participates in the APP hydrolysis process. Mutations in the PS1 gene () are the most common cause of early onset familial Alzheimer's disease (FAD). The mutations can alter the activity of γ-secretase on the cleavage of APP. Previous studies have shown that mutations increase the expression and activity of BACE1 and that BACE1 expression and activity are elevated in the brains of mutant knock-in mice, compared with wild-type mice, as well as in the cerebral cortex of FAD patients carrying mutations, compared with sporadic AD patients and controls. Here, we used a knockout cell line and a PS1 inhibitor to show that PS1 affects the expression of BACE1 in vitro. Furthermore, we used sucrose gradient fractionation combined with western blotting to analyze the distribution of BACE1, combined with a time-lapse technique to show that PS1 upregulates the distribution and trafficking of BACE1 in the endoplasmic reticulum, Golgi, and endosomes. More importantly, we found that the mutant S170F increases the distribution of BACE1 in the endoplasmic reticulum and changes the ratio of mature BACE1 in the trans-Golgi network. The effect of mutations on BACE1 may contribute to determining the phenotype of early onset FAD.