Lipid Membranes and β-Amyloid: A Harmful Connection

Gradual changes in steady-state levels of beta amyloid peptides (A beta) in the brain are considered as initial step in the amyloid cascade hypothesis of Alzheimer's disease (AD). A beta is a product of the secretase cleavage of the amyloid precursor protein and there is evidence that the membrane lipid environment may modulate secretase activity and alters its function. A beta disturbs membrane properties of artificial and isolated biological membranes and of plasma membranes in living cells. A beta induced changes in membrane fluidity could be explained by physico-chemical interactions of the peptide with membrane components such as cholesterol, phospholipids and gangliosides. Thus, cell membranes may be the location where the neurotoxic cascade of A beta is initiated. Perturbation of membranes, binding to lipids and alteration of cellular calcium signaling by A beta have been reported by several studies and these topics are examined in this review.