Lysosomal diseases pathogenesis

Other lines of evidence also support the notion that deregulated cholesterol homeostasis may contribute to the AD pathogenesis. AD patients have been reported to develop intracellular A/1 accumulation in the late endo-somes and lysosomes. Similar pathological features, including swollen late endosomes and A/ accumulation, have also been reported in Niemann-Pick type C disease patients [52,53], Npcl deficient mice as well as in mouse models of AD [54,55]. The Npcl gene product is essential for the mobihzation of cellular cholesterol. Excess cholesterol can be transported into endoplasmic reticulum and esterified by acyl co enzyme A cholesterol acyltransferase (ACAT) and stored in lipid droplets. Inhibition of ACAT activity has been reported to reduce A/3 levels in vitro and plaque pathology in animal models of AD [56,57]. 

Jeyakumar, M., Butters, T. D., Dwek, R. A., and Platt, F. M., Glycosphingolipid lysosomal storage diseases therapy and pathogenesis, Neuropathol Appl Neurobiol 28 (2002) 343-357. 

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