SOLUBLE BETA-AMYLOID INDUCTION OF ALZHEIMERS PHENOTYPE FOR HUMAN FIBROBLAST K+ CHANNELS

Although beta-amyloid is the main constituent of neurite plaques and m ay play a role in the pathophysiology of Alzheimer's disease, mechanis ms by which soluble beta-amyloid might produce early symptoms such as memory loss before diffuse plaque deposition have not been implicated. Treatment of fibroblasts with beta-amyloid (10 nM) induced the same p otassium channel dysfunction previously shown to occur specifically in fibroblasts from patients with Alzheimer's disease-namely, the absenc e of a 113-picosiemen potassium channel. A tetraethylammonium-induced increase of intracellular concentrations of calcium, [Ca2+]i, a respon se that depends on functional 113-picosiemen potassium channels. was a lso eliminated or markedly reduced by 10 nM beta-amyloid. Increased [C a2+]i induced by high concentrations of extracellular potassium and 16 6-picosiemen potassium channels were unaffected by 10 nM beta-amyloid. In Alzheimer's disease, then, beta-amyloid might alter potassium chan nels and thus impair neuronal function to produce symptoms such as mem ory loss by a means other than plaque formation.