Garlind A, Wiehager B, Winblad B, Fowler C J
Karolinska Institute, Department of Clinical Neuroscience and Family Medicine, Huddinge University Hospital, Sweden.
Neurobiol Aging. 1997 Sep-Oct;18(5):559-61. doi: 10.1016/s0197-4580(97)00039-0.
An increasing number of signal transduction disturbances have been reported in Alzheimer's disease. These changes are not restricted to histopathologically changed brain areas but are seen also in peripheral tissues. One of the most severe disturbances is a loss of calcium-mobilizing intracellular inositol(1,4,5)-trisphosphate receptors in Alzheimer cerebellar and cortical tissues. In the present study, the binding of [3H]inositol(1,4,5)trisphosphate ([3H]Ins(1,4,5)P3) to the calcium-mobilizing inositol(1,4,5)trisphosphate receptors in platelet membranes from eight Alzheimer's disease patients and eight control subjects were investigated to determine its possible role as a biological marker in Alzheimer's disease. It was found that there were no significant difference in [3H]Ins(1,4,5)P3 binding with respect to the number of sites measured at different protein concentrations or to the sensitivity of the binding to inhibition by nonradioactive Ins(1,4,5)P3 between Alzheimer disease platelets and controls. It is concluded that inositol(1,4,5)trisphosphate receptor levels are preserved in platelets from patients with Alzheimer's disease.
越来越多的信号转导紊乱已在阿尔茨海默病中被报道。这些变化不仅局限于组织病理学上发生改变的脑区,在外周组织中也可见到。最严重的紊乱之一是阿尔茨海默病患者小脑和皮质组织中动员钙的细胞内肌醇(1,4,5)-三磷酸受体的丧失。在本研究中,研究了[3H]肌醇(1,4,5)-三磷酸([3H]Ins(1,4,5)P3)与8例阿尔茨海默病患者和8例对照者血小板膜中动员钙的肌醇(1,4,5)-三磷酸受体的结合情况,以确定其作为阿尔茨海默病生物标志物的可能作用。结果发现,在不同蛋白质浓度下测量的[3H]Ins(1,4,5)P3结合位点数量,或阿尔茨海默病患者血小板与对照者之间结合对非放射性Ins(1,4,5)P3抑制的敏感性方面,均无显著差异。结论是,阿尔茨海默病患者血小板中的肌醇(1,4,5)-三磷酸受体水平保持不变。