SERUM-INDUCED AND BRADYKININ-INDUCED CALCIUM TRANSIENTS IN FAMILIAL ALZHEIMER FIBROBLASTS

The calcium-sensitive photoprotein, aequorin, was used to examine seru m- and bradykinin-induced transient increases in free cytosolic calciu m ions in skin fibroblasts from 10 individuals with early onset famili al AD (FAD), including four who were biopsied before their clinical sy mptoms would allow a diagnosis of AD, 2 individuals with late onset FA D, 8 at-risk but nonsymptomatic individuals, and 13 controls. The data show that (a) among controls, the peaks of the calcium transients inc rease in height as a function of donor age; (b) transients induced by 10% serum, 10 nM bradykinin (BK) or 100 nM BK were generally lower in FAD fibroblasts, including those from donors in the early stages of th e disease, than in age-matched control cells; (c) such transients are reduced in cells from a proportion of the nonsymptomatic, at-risk indi viduals. Thus, serum- and BK-induced calcium transients are reduced in fibroblasts from both early and more advanced stage FAD donors and pe rhaps even from donors who are presymptomatic carriers of the defectiv e gene. The data also suggest that changes in calcium transients in FA D fibroblasts neither minic nor exaggerate the effects of normal aging .