Martins R N, Turner B A, Carroll R T, Sweeney D, Kim K S, Wisniewski H M, Blass J P, Gibson G E, Gandy S
Department of Neurology and Neuroscience, Cornell University Medical College, New York NY 10021, USA.
Neuroreport. 1995 Dec 29;7(1):217-20.
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.
大多数早发性家族性阿尔茨海默病与14号染色体上的一种膜蛋白S182中的错义突变有关。我们研究了受S182（Glu246）影响个体和未受影响家庭成员的皮肤成纤维细胞中β淀粉样蛋白（Aβ）前体（AβPP）的代谢。所有细胞系中的稳态AβPP水平相似，在用佛波酯或血清刺激细胞后释放的可溶性AβPP的增加程度也相似。在所有研究的细胞系中，仅在单个S182（Glu246）细胞系的培养基中始终可检测到Aβ水平，这与某些S182突变细胞系可能在其条件培养基中积累Aβ的结论一致。需要对更多个体的细胞在其他条件下进行研究，以确定Aβ水平升高与S182突变之间的这种关联。
