Oxysterol-Induced Rearrangement of the Liquid-Ordered Phase: A Possible Link to Alzheimer's Disease?

Nearest-neighbor recognition measurements have been made for an exchangeable phospholipid (A) interacting with an exchangeable form of cholesterol (B) in host membranes derived from 1, 2-dipalmitoyl-sn-glycero-3-phosphocholine and varying concentrations of cholesterol, 7 beta-hydroxycholesterol (7 beta-OH), and 25-hydroxycholesterol (25-OH). Whereas partial replacement of cholesterol with 7 beta-OH strengthens the association between A and B, a similar substitution with 25-OH weakens this association. A model that accounts for this dichotomy, and the possible relevance of these findings to the cytotoxicity of 7 beta-OH and to Alzheimer's disease are briefly discussed.