Lombardi V R, García M, Cacabelow R
EuroEspes Biomedical Research Center, Division of Biotechnology, Bergondo, La Coruña, Spain.
Methods Find Exp Clin Pharmacol. 1998 Jun;20(5):377-86. doi: 10.1358/mf.1998.20.5.485697.
Recent advances in molecular genetics have suggested that genetic predisposition can be considered one of the most important risk factors for Alzheimer's disease (AD) development. A significant increase in the number of amyloid plaques in AD patients with an apolipoprotein E4 (APOE) allele has been observed and the results of several genetic studies indicate that the etiology of this neurodegenerative disease is associated with the presence of the allele E4 of APOE gene. A potential source of damage in the AD brain is an altered response triggered by microglial activation, which is associated with senile plaque formation. In this study, in vitro cell cultures were established to investigate the effect of different concentrations of human sera (2.5% and 10%) with specific APOE genotypes from Alzheimer and non-Alzheimer subjects on ameboid and flat microglial cells obtained from adult rat hippocampus. Results show that this in vitro test can be applied as an in vitro model to test specific responses of microglia to human sera as well as a primary screening procedure to evaluate the effect of novel compounds for the treatment of AD and neuroimmune-associated disorders.
分子遗传学的最新进展表明，遗传易感性可被视为阿尔茨海默病（AD）发展的最重要风险因素之一。已观察到携带载脂蛋白E4（APOE）等位基因的AD患者脑中淀粉样斑块数量显著增加，多项遗传学研究结果表明，这种神经退行性疾病的病因与APOE基因的E4等位基因的存在有关。AD大脑中潜在的损伤来源是由小胶质细胞激活引发的反应改变，这与老年斑的形成有关。在本研究中，建立了体外细胞培养体系，以研究来自阿尔茨海默病患者和非阿尔茨海默病患者的具有特定APOE基因型的不同浓度人血清（2.5%和10%）对从成年大鼠海马体获得的阿米巴样和扁平小胶质细胞的影响。结果表明，该体外试验可作为一种体外模型来测试小胶质细胞对人血清的特异性反应，以及作为一种初步筛选程序来评估新型化合物对AD和神经免疫相关疾病的治疗效果。
