Cholesterol depletion reduces aggregation of amyloid-beta peptide in hippocampal neurons

A key event in the pathogenesis of Alzheimer's disease is the conversion of soluble amyloid A beta-peptide into toxic aggregates. Here, we studied the effect of cholesterol depletion on the formation of insoluble A beta. We found that reduction of neuronal cholesterol by similar to 25% reduced the neuronal formation of insoluble A beta without affecting the secretion of soluble A beta. Moreover, we demonstrate that A beta-oligomers from Alzheimer's disease brains associate with a detergent-resistant membrane fraction in a cholesterol-dependent manner. These results suggest a key role for cholesterol in aggregation of A beta. (c) 2006 Elsevier Inc. All rights reserved.