CALCIUM RESPONSES IN HUMAN FIBROBLASTS - A DIAGNOSTIC MOLECULAR PROFILE FOR ALZHEIMERS-DISEASE

We have previously identified alterations of K+ channel function, IP3- mediated calcium release, and Cp20 (a memory-associated GTP binding pr otein) in fibroblasts from AD patients vs. controls. In the present st udy we introduce a scoring system based on these response alterations that integrates two or more alterations (and their degree) in AD vs. c ontrol fibroblasts. This scoring system generates an index that distin guishes AD patients from controls with both high specificity and sensi tivity. We also show that low doses of bradykinin elicit intracellular calcium release almost exclusively in AD cell lines in an all or none fashion that provide a clear measurement of enhanced IP3-mediated fun ction in AD vs. controls.