Scott R B, Collins J M, Hunt P A
Department of Internal Medicine, Medical College of Virginia/Virginia Commonwealth University, Richmond 23298-0287, USA.
Mech Ageing Dev. 1994 Jul;75(1):1-10. doi: 10.1016/0047-6374(94)90023-x.
Down Syndrome (DS) patients over the age of 40 have brain lesions identical to those of patients with Alzheimer's Disease (AD). We have earlier shown that with some membrane probes, the plasma membranes of circulating leukocytes had increased fluidity in AD compared to the normally more rigid membranes in similarly aged subjects. We next questioned whether the occurrence of AD-like pathological lesions in older DS subjects would be associated with a similar increase in membrane fluidity. Fluidity was assessed by measurements of steady-state fluorescence anisotropy using TMA-DPH, which anchors at the plasma membrane surface, and a series of 9-anthroyloxy fatty acids substituted with the fluorescent moiety at different positions on the fatty acid, which permit measurement of fluidity at different depths of the plasma membrane. This was done simultaneously in neutrophils, lymphocytes, and monocytes utilizing flow cytometry. In older DS subjects (average age 52.6), plasma membrane fluidity was indeed increased, a finding similar to that with AD leukocytes. Membrane fluidity of leukocytes of young DS subjects (average age 23.6 years) was less than that seen in older subjects. Membrane changes may result from lipophilic substances released from the central nervous system, or may reflect intrinsic differences in membrane structure unique in DS.
40岁以上的唐氏综合征（DS）患者存在与阿尔茨海默病（AD）患者相同的脑损伤。我们之前已经表明，使用一些膜探针时，与年龄相仿的正常受试者相比，AD患者循环白细胞的质膜流动性增加，而正常受试者的质膜通常更僵硬。接下来，我们质疑老年DS受试者中出现的AD样病理损伤是否会伴随着膜流动性的类似增加。使用锚定在质膜表面的TMA-DPH以及一系列在脂肪酸不同位置被荧光部分取代的9-蒽氧基脂肪酸来测量稳态荧光各向异性，以此评估膜流动性，这些9-蒽氧基脂肪酸能够测量质膜不同深度处的流动性。利用流式细胞术同时在中性粒细胞、淋巴细胞和单核细胞中进行此项操作。在老年DS受试者（平均年龄52.6岁）中，质膜流动性确实增加了，这一发现与AD白细胞的情况相似。年轻DS受试者（平均年龄23.6岁）白细胞的膜流动性低于老年受试者。膜变化可能是由中枢神经系统释放的亲脂性物质引起的，也可能反映了DS中独特的膜结构内在差异。
