Regenerative and Restorative Medical Research Center, Istanbul Medipol University, Istanbul, Turkey.
Department of Medical Biochemistry, Faculty of Medicine, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey.
Curr Alzheimer Res. 2019;16(7):613-621. doi: 10.2174/1567205016666190730155926.
CA1 subregion of the hippocampal formation is one of the primarily affected structures in AD, yet not much is known about proteome alterations in the extracellular milieu of this region.
In this study, we aimed to identify the protein expression alterations throughout the pre-pathological, progression and pathological stages of AD mouse model.
The CA1 region perfusates were collected by in-vivo intracerebral push-pull perfusion from transgenic 5XFAD mice and their non-transgenic littermates at 3, 6 and 12 wereβmonths of age. Morris water maze test and immunohistochemistry staining of A performed to determine the stages of the disease in this mouse model. The protein expression differences were analyzed by label-free shotgun proteomics analysis.
A total of 251, 213 and 238 proteins were identified in samples obtained from CA1 regions of mice at 3, 6 and 12 months of age, respectively. Of these, 68, 41 and 33 proteins showed statistical significance. Pathway analysis based on the unique and common proteins within the groups revealed that several pathways are dysregulated during different stages of AD. The alterations in glucose and lipid metabolisms respectively in pre-pathologic and progression stages of the disease, lead to imbalances in ROS production via diminished SOD level and impairment of neuronal integrity.
We conclude that CA1 region-specific proteomic analysis of hippocampal degeneration may be useful in identifying the earliest as well as progressional changes that are associated with Alzheimer's disease.
海马结构的 CA1 亚区是 AD 中受影响最严重的结构之一，但对于该区域细胞外基质中的蛋白质组变化知之甚少。
本研究旨在鉴定 AD 小鼠模型的预病理、进展和病理阶段整个过程中的蛋白表达变化。
通过活体脑室内推挽灌流从转 5XFAD 小鼠及其非转基因同窝仔鼠的 CA1 区采集灌流液，分别在 3、6 和 12 月龄时进行 Morris 水迷宫测试和 Aβ免疫组化染色，以确定该小鼠模型疾病的阶段。通过无标记 shotgun 蛋白质组学分析来分析蛋白表达差异。
分别从 3、6 和 12 月龄的小鼠 CA1 区获得的样本中鉴定出 251、213 和 238 种蛋白质，其中 68、41 和 33 种蛋白质具有统计学意义。基于各组内独特和共同蛋白质的通路分析显示，在 AD 的不同阶段有几个通路发生失调。在疾病的预病理和进展阶段，葡萄糖和脂质代谢的改变分别导致 SOD 水平降低和神经元完整性受损，从而导致 ROS 产生失衡。
我们得出结论，海马退变的 CA1 区特异性蛋白质组分析可能有助于鉴定与阿尔茨海默病相关的最早和进展性变化。
