Cholesterol depletion inhibits the degradation of amyloid β-peptide in rat pheochromocytoma (PC12) cells

Abstract: Amyloid β-peptide (Aβ) is a very important pathogenic factor for Alzheimer''s disease (AD). It is a constitutive product of cellular metabolism and occurs in normal biological fluids, such as CSF and plasma. As the steady state levels of all peptides in vivo are a direct consequence of the balance between their anabolism and catabolism, peptide accumulation can arise not only from increased production but also from decreased breakdown. Although increasing evidence indicates that cholesterol is a risk factor for AD development, the exact mechanisms of cholesterol on Aβ metabolism or deposition have remained unclear. Here, we focus our attention on the effect of cholesterol depletion on the degradation of Aβ1–40. Cholesterol depletion of cultured rat pheochromocytoma (PC12) cells was achieved by methyl-β-cyclodextrin (MβCD) extraction. It was found that cholesterol depletion by MβCD extraction can suppress Aβ degradation in PC12 cells. [Copyright &y& Elsevier]