Mild cholesterol depletion reduces amyloid-beta production by impairing APP trafficking to the cell surface.

ABSTRACT: It has been suggested that cellular cholesterol levels can modulate the metabolism of the amyloid precursor protein (APP) but the underlying mechanism remains controversial. In the current study, we investigate in detail the relationship between cholesterol reduction, APP processing and gamma-secretase function in cell culture studies. We found that mild membrane cholesterol reduction led to a decrease in Abeta(40) and Abeta(42) in different cell types. We did not detect changes in APP intracellular domain or Notch intracellular domain generation. Western blot analyses showed a cholesterol-dependent decrease in the APP C-terminal fragments and cell surface APP. Finally, we applied a fluorescence resonance energy transfer (FRET)-based technique to study APP-Presenilin 1 (PS1) interactions a

SUBMITTER: Guardia-Laguarta C 

PROVIDER: S-EPMC2741735 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature