Niemann-Pick disease type C (NPC) is a rare hereditary neurodegenerative disorder, caused by mutations in the NPC1 or NPC2 gene. It is characterised by accumulation of free cholesterol and other lipids and has a number of pathological similarities with complex Alzheimer's disease (AD). In our previous studies, increased activity of BACE1, the key enzyme of AD, was found in NPC mouse models. Therefore, the aim of this dissertation was to explore the molecular background of the observed effect and examine the effect of BACE1 inhibition on the pathological characteristics of the disease. In addition, the goal was to determine the earliest lipid changes responsible for the differences in brain region vulnerability and endosomal dysfunction in NPC disease by lipidome analysis. Primary neuronal cell cultures, organotipic brain slice cultures, and hippocampus and cerebellum of mice that have a spontaneous mutation in NPC1 gene and do not synthesize the NPC1 protein (NPC1 mice) and wild type mice (wt) were used. NPC1 neurons showed increased proteolysis of BACE1 substrates- Sez6L and Sez6 compared with wt neurons. Immunocytochemical analysis demonstrated accumulation of the aforementioned substrates in early endosomes of NPC1 neurons. The altered localization of Sez6 and Sez6L in early endosomes was confirmed by endolysosome fractionation in the hippocampus and cerebellum of NPC1 mice. Interestingly, treatment with a BACE1 inhibitor partially ameliorated the pathological features of NPC disease, including reduction in the accumulation of Sez6 and Sez6L, reduction in the size of early endosome vesicles, reduction in total tau protein level in NPC1 neurons, and reduction in neuroinflammation (activation of astrocytes and microglia) in cortico-hippocampal brain slices from NPC1 mice. Lipidome analysis revealed that even in the asymptomatic phase of the disease, there are significant differences in the distribution and content of certain lipids between NPC1 and wt mice in the cerebellum and hippocampus, and in early endosomes. These studies provide evidence for a possible role of the BACE1 protease and its substrates in the pathogenesis of NPC disease. The observed changes in the lipid composition of brain regions and early endosomes may contribute to the development of the pathological features of NPC disease.