Background:Microcirculatory factors play an important role in amyloid-β (Aβ)-related neuropathology in Alzheimer’s disease (AD). Transgenic (Tg) rat models of mutant Aβ deposition can enhance our understanding of this microvascular pathology. Objective:Here we report stereology-based quantificationand comparisons (between- and within-group) of microvessel length and number and associated parameters in hippocampal subregions in Tg model of AD in Fischer 344 rats and non-Tg littermates. Methods:Systematic-random samples of tissue sections were processed and laminin immunostained to visualize microvessels through the entire hippocampus in Tg and non-Tg rats. A computer-assisted stereology system was used to quantify microvessel parameters including total number, total length, and associated densities in dentate gyrus (DG) and cornu ammonis (CA) subregions. Results:Thin hair-like capillaries are common near Aβ plaques in hippocampal subregions of Tg rats. There are a 53% significant increase in average length per capillary across entire hippocampus (p≤0.04) in Tg compared to non-Tg rats; 49% reduction in capillary length in DG (p≤0.02); and, higher microvessel density in principal cell layers (p≤0.03). Furthermore, within-group comparisons confirm Tg but not non-Tg rats have significant increase in number density (p≤0.01) and potential diffusion distance (p≤0.04) of microvessels in principal cell layers of hippocampal subregions. Conclusion:We show the Tg deposition of human Aβ mutations in rats disrupts the wild-type microanatomy of hippocampal microvessels. Stereology-based microvascular parameters could promote the development of novel strategies for protection and the therapeutic management of AD.

中文翻译：

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阿尔茨海默病转基因大鼠模型海马微血管参数的立体变化

背景：微循环因子在阿尔茨海默病 (AD) 的淀粉样蛋白 β (Aβ) 相关神经病理学中起重要作用。突变 Aβ 沉积的转基因 (Tg) 大鼠模型可以增强我们对这种微血管病理学的理解。目的：在此我们报告了基于体视学的 Fischer 344 大鼠和非 Tg 同窝仔鼠 Tg 模型中海马亚区微血管长度和数量以及相关参数的体视学量化和比较（组间和组内）。方法：对组织切片的系统随机样本进行处理和层粘连蛋白免疫染色，以观察 Tg 和非 Tg 大鼠整个海马的微血管。计算机辅助体视系统用于量化微血管参数，包括总数、总长度、以及齿状回 (DG) 和玉米角 (CA) 子区域的相关密度。结果：Tg大鼠海马亚区Aβ斑块附近常见细毛状毛细血管。与非 Tg 大鼠相比，Tg 中整个海马体的每根毛细血管平均长度显着增加了 53%（p≤0.04）；DG 毛细管长度减少 49% (p≤0.02)；并且，主细胞层中的微血管密度更高（p≤0.03）。此外，组内比较证实了 Tg 而非非 Tg 大鼠在海马亚区主要细胞层中微血管的数量密度（p≤0.01）和潜在扩散距离（p≤0.04）显着增加。结论：我们发现大鼠中人类 Aβ 突变的 Tg 沉积破坏了海马微血管的野生型显微解剖结构。