POTASSIUM CHANNEL DYSFUNCTION IN FIBROBLASTS IDENTIFIES PATIENTS WITHALZHEIMER-DISEASE

Since memory loss is characteristic of Alzheimer disease (AD), and sin ce K+ channels change during acquisition of memory in both molluscs an d mammals, we investigated K+ channel function as a possible site of A D pathology and, therefore, as a possible diagnostk index as well. A 1 13-pS tetraethylammonium (TEA)-sensftive K+ channel was consistendy ab sent from AD ribroblasts, while it was often present in young and aged control fibroblasts. A second (166-pS) K+ channel was present in all three groups. Elevated external potassium raised intracellular Ca2+ in all cases. TEA depolarized and caused intracellular Ca2+ elevation in young and aged control fibroblasts but not AD fibroblasts. The invari able absence of a 113-pS TEA-sensitive K+ channel and TEA-induced Ca2 signal indicate K+ channel dysfunction in AD fibroblasts. These resul ts suggest the possibility of a laboratory method that would diagnosti cally distinguish AD patients, with or without a family history of AD, from normal age-matched controls and also from patients with non-AD n eurological and psychiatric disorders.