High levels of amyloid-beta protein from S182 (Glu246) familial Alzheimer's cells.

Most early-onset familial Alzheimer disease is associated with missense mutations in S182, a membrane protein on chromosome 14. We investigated amyloid-beta protein (A beta) precursor (A beta PP) metabolism in skin fibroblasts from S182 (Glu246)-affected individuals and unaffected family members. Steady-state A beta PP levels were similar among all lines as was the degree of increase in soluble A beta PP released upon stimulation of cells with either phorbol ester or serum. Among all lines studied, A beta levels were consistently detectable only in the medium of a single line of S182 (Glu246) cells, consistent with the conclusion that some S182 mutant lines may accumulate A beta in their conditioned media. Studies of cells from additional individuals and under other conditions will be required to establish this association of elevated A beta levels with S182 mutations.