Wisniewski T, Dowjat W K, Buxbaum J D, Khorkova O, Efthimiopoulos S, Kulczycki J, Lojkowska W, Wegiel J, Wisniewski H M, Frangione B
Department of Neurology, New York University Medical Center, NY 10016, USA.
Neuroreport. 1998 Jan 26;9(2):217-21. doi: 10.1097/00001756-199801260-00008.
The majority of early-onset familial Alzheimer's disease (FAD) is associated with mutations in the presenilin-1 (PS1) gene. We describe a novel Polish PS1 mutation of Pro117Leu, associated with the earliest average age of onset and death so far reported in a PS-linked, FAD kindred. Human kidney 293 and mouse neuroblastoma N2a cells were stably transfected with wild-type and PS1 P117L. There was a significant increase in the amyloid beta42/40 ratio in the N2a P117L PS1 transfected cells compared with N2a transfected with wild-type PS1. What role PS has in the pathogenesis of AD remains to be determined, however, the severity of the clinical picture associated with this PS1 mutation stresses the importance of presenilin.
大多数早发性家族性阿尔茨海默病（FAD）与早老素-1（PS1）基因的突变有关。我们描述了一种新的波兰PS1突变，即Pro117Leu，它与迄今为止在一个与PS相关的FAD家族中报道的最早平均发病年龄和死亡年龄相关。用野生型和PS1 P117L稳定转染人肾293细胞和小鼠神经母细胞瘤N2a细胞。与转染野生型PS1的N2a细胞相比，转染PS1 P117L的N2a细胞中淀粉样β42/40比值显著增加。然而，PS在AD发病机制中起什么作用仍有待确定，不过，与这种PS1突变相关的临床症状的严重性强调了早老素的重要性。
