Carrera Ivan, Etcheverria Ignacio, Li Yi, Fernandez-Novoa Lucia, Lombardi Valter, Vigo Carmen, Palacios Hector H, Benberin Valery V, Cacabelos Ramon, Aliev Gjumrakch
Department of Neurosciences, EuroEspes Biotechnology, La Coruna, Spain.
Yale University School of Medicine, New Haven, CT.
Cent Asian J Glob Health. 2014 Mar 27;2(Suppl):119. doi: 10.5195/cajgh.2013.119. eCollection 2013.
APP/PS1 double-transgenic mouse models of Alzheimer's disease (AD), which overexpress mutated forms of the gene for the human amyloid precursor protein (APP) and presenilin 1 (PS1), have provided robust neuropathological hallmarks of an AD-like pattern at early ages. This study aimed to characterize immunocytochemical patterns of the AD mouse brain, which is treated with the EB101 vaccine, as a model for human AD.
In this novel vaccine, a new approach has been taken to circumvent past failures with A vaccines by judiciously selecting an adjuvant consisting of a physiological matrix embedded in liposomes, composed of naturally occurring phospholipids (phosphatidylcholine, phosphatidylglycerol, and cholesterol).
Our findings showed that the administration of amyloid-1-42 (A) and sphingosine-1-phosphate emulsified in liposome complex (EB101) to APP/PS1 mice before the onset of A brain deposition (at 7 weeks of age) and/or at an older age (35 weeks of age) can be effective in both halting the progression and clearing the AD-like neuropathological hallmarks. In addition, passive immunization with EB101 did not activate inflammatory responses from the immune system and astrocytes. Consistent with a decreased inflammatory background, the basal immunological interaction between the T cells and the affected areas (hippocampus) in the brain of treated mice was notably reduced.
These results provide strong evidence that immunization with the EB101 vaccine prevents and attenuates AD neuropathology in this type of double-transgenic mice.
阿尔茨海默病（AD）的APP/PS1双转基因小鼠模型过度表达人类淀粉样前体蛋白（APP）和早老素1（PS1）基因的突变形式，在幼年时就出现了类似AD模式的强大神经病理学特征。本研究旨在表征经EB101疫苗治疗的AD小鼠脑的免疫细胞化学模式，作为人类AD的模型。
在这种新型疫苗中，采用了一种新方法来规避过去A疫苗的失败，即明智地选择一种由嵌入脂质体的生理基质组成的佐剂，该脂质体由天然存在的磷脂（磷脂酰胆碱、磷脂酰甘油和胆固醇）组成。
我们的研究结果表明，在A脑沉积开始前（7周龄）和/或老年（35周龄）向APP/PS1小鼠施用脂质体复合物（EB101）乳化的淀粉样蛋白-1-42（A）和鞘氨醇-1-磷酸，在阻止疾病进展和清除类似AD的神经病理学特征方面均有效。此外，用EB101进行被动免疫不会激活免疫系统和星形胶质细胞的炎症反应。与炎症背景降低一致，治疗小鼠脑中T细胞与受影响区域（海马体）之间的基础免疫相互作用显著减少。
这些结果提供了强有力的证据，证明用EB101疫苗免疫可预防和减轻这种双转基因小鼠的AD神经病理学。
