Etcheberrigaray R, Hirashima N, Nee L, Prince J, Govoni S, Racchi M, Tanzi R E, Alkon D L
Laboratory of Applied Neuroscience, Georgetown University Medical Center, NW Washington, DC 20007, USA.
Neurobiol Dis. 1998 Jul;5(1):37-45. doi: 10.1006/nbdi.1998.0176.
We have previously identified alterations of K+ channel function, IP3-mediated calcium release, and Cp20 (a memory-associated GTP binding protein) in fibroblasts from Alzheimer's disease (AD) patients vs controls. Some of these alterations can be integrated into an index that distinguishes AD patients from controls with both high specificity and high sensitivity. We report here that alterations in IP3-mediated calcium responses are present in a large proportion of AD family members (i.e., individuals at high risk) before clinical symptoms of Alzheimer's disease are present. This was not the case if such members later "escaped" AD symptoms. This preclinical calcium signal correlate of later AD does not reflect, however, the presence of the PS1 familial AD gene.
我们之前已经确定，与对照组相比，阿尔茨海默病（AD）患者成纤维细胞中的钾离子通道功能、肌醇三磷酸（IP3）介导的钙释放以及Cp20（一种与记忆相关的GTP结合蛋白）存在改变。其中一些改变可以整合到一个指标中，该指标能够以高特异性和高灵敏度区分AD患者与对照组。我们在此报告，在阿尔茨海默病临床症状出现之前，很大一部分AD家族成员（即高危个体）存在IP3介导的钙反应改变。如果这些成员后来“未出现”AD症状，则情况并非如此。然而，这种后期AD的临床前钙信号相关性并不反映PS1家族性AD基因的存在。
