Department of Psychological Sciences, University of Missouri, Columbia, Missouri, United States of America.
Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, Missouri, United States of America.
PLoS One. 2018 Apr 11;13(4):e0195469. doi: 10.1371/journal.pone.0195469. eCollection 2018.
Transgenic rat models of Alzheimer's disease were used to examine differences in memory and brain histology. Double transgenic female rats (APP+PS1) over-expressing human amyloid precursor protein (APP) and presenilin 1 (PS1) and single transgenic rats (APP21) over-expressing human APP were compared with wild type Fischer rats (WT). The Barnes maze assessed learning and memory and showed that both APP21 and APP+PS1 rats made significantly more errors than the WT rats during the acquisition phase, signifying slower learning. Additionally, the APP+PS1 rats made significantly more errors following a retention interval, indicating impaired memory compared to both the APP21 and WT rats. Immunohistochemistry using an antibody against amyloid-β (Aβ) showed extensive and mostly diffuse Aβ plaques in the hippocampus and dense plaques that contained tau in the cortex of the brains of the APP+PS1 rats. Furthermore, the APP+PS1 rats also showed vascular changes, including cerebral amyloid angiopathy with extensive Aβ deposits in cortical and leptomeningeal blood vessel walls and venous collagenosis. In addition to the Aβ accumulation observed in arterial, venous, and capillary walls, APP+PS1 rats also displayed enlarged blood vessels and perivascular space. Overall, the brain histopathology and behavioral assessment showed that the APP+PS1 rats demonstrated behavioral characteristics and vascular changes similar to those commonly observed in patients with Alzheimer's disease.
阿尔茨海默病的转基因大鼠模型被用于研究记忆和脑组织学的差异。过表达人淀粉样前体蛋白（APP）和早老素 1（PS1）的双转基因雌性大鼠（APP+PS1）和过表达人 APP 的单转基因大鼠（APP21）与野生型 Fischer 大鼠（WT）进行了比较。Barnes 迷宫评估了学习和记忆，结果表明，在获得阶段，APP21 和 APP+PS1 大鼠的错误明显多于 WT 大鼠，表明学习速度较慢。此外，与 APP21 和 WT 大鼠相比，APP+PS1 大鼠在保留间隔后犯的错误明显更多，表明记忆力受损。用针对淀粉样蛋白-β（Aβ）的抗体进行免疫组织化学染色显示，APP+PS1 大鼠的海马体中存在广泛的且主要是弥漫性的 Aβ 斑块，皮质中存在含有 tau 的密集斑块。此外，APP+PS1 大鼠还表现出血管变化，包括大脑淀粉样血管病，皮质和软脑膜血管壁以及静脉胶原病中广泛存在 Aβ 沉积。除了在动脉、静脉和毛细血管壁中观察到的 Aβ 积累外，APP+PS1 大鼠还显示出血管扩张和血管周围空间增大。总的来说，脑组织病理学和行为评估表明，APP+PS1 大鼠表现出与阿尔茨海默病患者常见的行为特征和血管变化相似的特征。
