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 mumol 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 mumol L-1). Moreover, beta 1-40 and its two fragments induced a significant alteration of 45Ca 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 Ca(2+)-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.