Soluble beta-amyloid induction of Alzheimer's phenotype for human fibroblast K+ channels

Science. 1994 Apr 8;264(5156):276-9. doi: 10.1126/science.8146663.


Although beta-amyloid is the main constituent of neurite plaques and may play a role in the pathophysiology of Alzheimer's disease, mechanisms 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 potassium channel dysfunction previously shown to occur specifically in fibroblasts from patients with Alzheimer's disease--namely, the absence of a 113-picosiemen potassium channel. A tetraethylammonium-induced increase of intracellular concentrations of calcium, [Ca2+]i, a response that depends on functional 113-picosiemen potassium channels, was also eliminated or markedly reduced by 10 nM beta-amyloid. Increased [Ca2+]i induced by high concentrations of extracellular potassium and 166-picosiemen potassium channels were unaffected by 10 nM beta-amyloid. In Alzheimer's disease, then, beta-amyloid might alter potassium channels and thus impair neuronal function to produce symptoms such as memory loss by a means other than plaque formation.

Publication types

  • Comparative Study

MeSH terms

  • Alzheimer Disease / metabolism*
  • Amyloid beta-Peptides / pharmacology*
  • Bombesin / pharmacology
  • Calcium / metabolism
  • Cell Line
  • Cells, Cultured
  • Dimethyl Sulfoxide / pharmacology
  • Female
  • Fibroblasts / drug effects*
  • Fibroblasts / metabolism
  • Humans
  • Male
  • Phenotype
  • Potassium Channel Blockers
  • Potassium Channels / drug effects*
  • Potassium Channels / metabolism
  • Potassium Chloride / pharmacology
  • Solubility
  • Tetraethylammonium
  • Tetraethylammonium Compounds / pharmacology


  • Amyloid beta-Peptides
  • Potassium Channel Blockers
  • Potassium Channels
  • Tetraethylammonium Compounds
  • Tetraethylammonium
  • Potassium Chloride
  • Bombesin
  • Calcium
  • Dimethyl Sulfoxide