Amyloid beta peptide membrane perturbation is the basis for its biologicaleffects

Experimental studies have indicated that the mechanisms offered for explain ing the neurotoxicity of amyloid beta peptide (A beta P) are diverse, and i nclude altered enzyme activities, disrupted calcium homeostasis, and increa sed free radical formation. A beta P appears to interact at the cell membra ne with a multitude of receptor sites and also inserts physically into the membrane matrix. This membrane insertion affects the membrane fluidity and potentially influences the function of resident membrane proteins. We propo se a unifying hypothesis to explain the experimental observations of the di verse cellular responses to A beta P. The indiscriminate physical insertion of A beta P into the cell membrane unspecifically activates a host of memb rane processes by perturbation of the membrane proteins. This recurrent act ivation of membrane processes eventually culminates in neuronal cell death. We recommend that successful therapeutic interventions should be directed at reducing or preventing the interaction of A beta P with neuronal cell me mbranes.