Cholesterol modulates the membrane-disordering effects of beta-amyloid peptides in the hippocampus: Specific changes in Alzheimer's disease

Cholesterol represents an important determinant of the physical state of bi ological membranes, In Alzheimer's disease (AD) brains, specific changes in the distribution of cholesterol and its membrane-ordering effects take pla ce. In the present study, membrane fluidity was investigated at the level o f the hydrocarbon core and of the heads of the phospholipid bilayers using two different fluorescent probes, Hippocampal membranes of AD brains showed a reduced fluidity in the hydrocarbon core region only. Fluidity was corre lated with the cholesterol content in AD and control membranes, Aggregated beta-amyloid peptides (A beta) disrupted brain membrane structure in AD pat ients and controls in the sa me fashion. However, this effect was correlate d with the cholesterol content in AD membranes only, It is suggested that i n AD the brain becomes specifically sensitive for the modulation by membran e-bound cholesterol of the membrane-disturbing and ultimately neurotoxic pr operties of A beta. Copyright (C) 2000 S. Karger AG, Basel.