CALCIUM RESPONSES IN FIBROBLASTS FROM ASYMPTOMATIC MEMBERS OF ALZHEIMERS-DISEASE FAMILIES

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 Alzheimer's disease (AD) patients vs contro ls. Some of these alterations can be integrated into an index that dis tinguishes AD patients from controls with both high specificity and hi gh sensitivity. We report here that alterations in IP3-mediated calciu m responses are present in a large proportion of AD family members (i. e., individuals at high risk) before clinical symptoms of Alzheimer's disease are present. This was not the case if such members later ''esc aped'' AD symptoms. This preclinical calcium signal correlate of later AD does not reflect, however, the presence of the PSI familial AD gen e. (C) 1998 Academic Press.