The study of astrocytes and its role in the development and evolution of neurodegenerative diseases, including Alzheimer’s disease (AD) is essential to fully understand their aetiology. The aim if this study is to deepen into the concept of the heterogeneity of astrocyte subpopulations in the EC and in particular the identification of differentially functioning astrocyte subpopulations that respond differently to AD progression. S100β protein belongs to group of small calcium regulators of cell membrane channels and pumps that are expressed by astrocytes and is hypothesised to play and have a relevant role in AD development. We analysed the selective differentiation of S100β-positive astrocytes into Glutamine synthetase (GS) and Glial fibrillary acidic protein (GFAP)-positive sub-groups in the entorhinal cortex (EC) of AD triple transgenic animal model (3xTg-AD). EC is the brain region earliest affected in humans AD but also in this closest animal model regarding their pathology and time course. We observed no changes in the number of S100β-positive astrocytes between 1 and 18 months of age in the EC of 3xTg-AD mice. However, we identified relevant morphological changes in S100β/GFAP positive astrocytes showing a significant reduction in their surface and volume whilst an increase in number and percentage. Furthermore, the percentage of S100β/GS positive astrocyte population was also increased in 18 months old 3xTg-AD mice compared to the non-Tg mice. Our findings reveal the presence of differentially controlled astrocyte populations that respond differently to AD progression in the EC of 3xTg-AD mice. These results highpoints the major astrocytic role together with its early and marked affection in AD and arguing in favour of its importance in neurogenerative diseases and potential target for new therapeutic approaches.

对星形胶质细胞及其在神经退行性疾病（包括阿尔茨海默氏病（AD））的发展和进化中的作用的研究对于充分了解其病因学至关重要。本研究的目的是深化 EC 中星形胶质细胞亚群异质性的概念，特别是识别对 AD 进展反应不同的功能差异的星形胶质细胞亚群。S100β 蛋白属于由星形胶质细胞表达的细胞膜通道和泵的小钙调节剂组，被认为在 AD 发展中发挥并具有相关作用。我们分析了 AD 三重转基因动物模型 (3xTg-AD) 内嗅皮质 (EC) 中 S100β 阳性星形胶质细胞选择性分化为谷氨酰胺合成酶 (GS) 和胶质纤维酸性蛋白 (GFAP) 阳性亚群。EC 是人类 AD 中最早受影响的大脑区域，但在病理学和时间进程方面也是最接近的动物模型中受影响的大脑区域。我们观察到 3xTg-AD 小鼠 EC 中 1 至 18 个月龄期间 S100β 阳性星形胶质细胞的数量没有变化。然而，我们发现了 S100β/GFAP 阳性星形胶质细胞的相关形态变化，显示其表面和体积显着减少，而数量和百分比增加。此外，与非 Tg 小鼠相比，18 个月大的 3xTg-AD 小鼠中 S100β/GS 阳性星形胶质细胞群体的百分比也有所增加。我们的研究结果揭示了 3xTg-AD 小鼠 EC 中存在差异控制的星形胶质细胞群，它们对 AD 进展的反应不同。这些结果强调了星形胶质细胞的主要作用及其在 AD 中的早期和显着影响，并支持其在神经生成疾病中的重要性和新治疗方法的潜在目标。