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

Abstract

A key event in the pathogenesis of Alzheimer's disease is the conversion of soluble amyloid Aβ-peptide into toxic aggregates. Here, we studied the effect of cholesterol depletion on the formation of insoluble Aβ. We found that reduction of neuronal cholesterol by ∼25% reduced the neuronal formation of insoluble Aβ without affecting the secretion of soluble Aβ. Moreover, we demonstrate that Aβ-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 Aβ.

Keywords

• Cholesterol
• Aggregation
• Hippocampal neurons
• Aβ
• Oligomers
• Alzheimer's disease