High levels of amyloid-beta protein from S182 (Glu(246)) familial Alzheimer's cells
High levels of amyloid-beta protein from S182 (Glu(246)) familial Alzheimer's cells
复制标题
DOI：
10.1097/00001756-199512290-00052
复制
发表时间：
1995-12-29
期刊：
影响因子：
1.7
通讯作者：
Gandy, S
中科院分区：
文献类型：
--
作者：
Martins, RH;Turner, BA;Gandy, S
大多数早发性家族性阿尔茨海默病与S182错义突变有关，S182是14号染色体上的一种膜蛋白。我们研究了S182(Glu(246))患者和未受影响的家庭成员皮肤成纤维细胞的淀粉样β蛋白(Aβ)前体(AβPP)代谢。在所有细胞系中，稳态AβPP水平与佛波酯或血清刺激细胞时释放的可溶性AβPP的增加程度相似。在所研究的所有品系中，Aβ水平仅在S182(G1u(246))细胞的单个品系的培养液中持续可检测到，这与一些S182突变品系可能在其条件培养液中积累Aβ的结论一致。需要对其他个体和其他条件下的细胞进行研究，以确定Aβ水平升高与S182突变之间的这种联系。
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 (Glu(246))-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 (G1u(246)) 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.