ALZHEIMER AMYLOID BETA-PEPTIDES EXHIBIT IONOPHORE-LIKE PROPERTIES IN HUMAN ERYTHROCYTES

There is growing evidence that the amyloid beta-peptide (beta(1-40)) is involved in the aetiology of Alzheimer's disease also implicating an altered calcium homeostasis of affected cells. Beta(1-40) has been proposed to form calcium channels in synthetic bilayer membranes [1]. We wanted to investigate in the present study whether beta(1-40) (or fragments thereof) could act as ionophores in a biological membrane like the one in human erythrocytes. Incubation of the cells for 2 h and 4 h at 37 degrees C together with 6 mu mol L(-1) of beta(1-40) or of fragments beta(1-28) and beta(25-35), resulted in a significantly decreased energy charge qualitatively similar to the one obtained by a known calcium ionophore (A 23187, 0.05 mu mol L(-1)). Moreover, beta(1-40) and its two fragments induced a significant alteration of Ca-45 permeability in human red blood cells of the same type as the one achieved by the calcium ionophore. The ionophoric action of beta(1-40) and its two fragments may lead to an increase of the intracellular calcium ion concentration, in turn resulting in enhanced Ca2+-ATPase activity and a decrease in energy charge. This may be valid also for neuronal plasma membranes and could, therefore, be a possible aetiological mechanism in Alzheimer's disease.