engleski

Cholesterol accumulation upon NPC1 dysfunction alters trafficking of APP/C99

Cholesterol accumulation upon loss of NPC1 function leads to altered APP processing causing increased C99 and Abeta formation, the causative factor of Alzheimer's disease. The goal of our work was to investigate whether altered APP processing in NPC disease could be due to cholesterol-mediated trafficking defect of APP. To test this we analyzed subcellular distribution of endogenous APP/C99 in CHOwt and CHO NPC1-null cells by subcellular fractionation and confocal microscopy. We found that APP trafficking is disturbed in NPC cells and that both localization of APP and C99 is shifted towards early/late endosomal compartments. Our results suggest that increased formation of Abeta upon cholesterol accumulation in NPC disease may be due to increased subcellular localization of APP in endocytic pathway.

Alzheimer's disease; cholesterol; APP protein; Abeta peptide; neurodegeneration

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