Functional Neuroanatomy Group; IKERBASQUE, Basque Foundation for Science, Department of Neurosciences, Medical Faculty, University of the Basque Country (UPV/EHU), 48009/48940, Bilbao/Leioa, Vizcaya, Spain.
Laboratory of Molecular Cell Biomedicine, Department of Biology, University of the Balearic Islands, 07122, Palma, Spain.
Brain Struct Funct. 2023 Dec;228(9):2103-2113. doi: 10.1007/s00429-023-02707-x. Epub 2023 Sep 20.
Pathophysiology of sporadic Alzheimer's disease (SAD) and familial Alzheimer's disease (FAD) remains poorly known, including the exact role of neuroglia and specifically astroglia, in part because studies of astrocytes in human Alzheimer's disease (AD) brain samples are scarce. As far as we know, this is the first study of a 3-D immunohistochemical and microstructural analysis of glial fibrillary acidic protein (GFAP)- and glutamine synthetase (GS)-positive astrocytes performed in the entorhinal cortex (EC) of human SAD and FAD samples. In this study, we report prominent atrophic changes in GFAP and GS astrocytes in the EC of both SAD and FAD characterised by a decrease in area and volume when compared with non-demented control samples (ND). Furthermore, we did not find neither astrocytic loss nor astrocyte proliferation or hypertrophy (gliosis). In contrast with the astrogliosis classically accepted hypothesis, our results show a highly marked astrocyte atrophy that could have a major relevance in AD pathological processes being fundamental and key for AD mnesic and cognitive alterations equivalent in both SAD and FAD.
散发性阿尔茨海默病（SAD）和家族性阿尔茨海默病（FAD）的病理生理学仍然知之甚少，包括神经胶质，特别是星形胶质细胞的确切作用，部分原因是对人类阿尔茨海默病（AD）脑样本中星形胶质细胞的研究很少。据我们所知，这是首次在 SAD 和 FAD 样本的内嗅皮层（EC）中进行 3-D 免疫组织化学和神经胶质纤维酸性蛋白（GFAP）和谷氨酰胺合成酶（GS）阳性星形胶质细胞的微观结构分析。在这项研究中，我们报告了 SAD 和 FAD 患者 EC 中 GFAP 和 GS 星形胶质细胞的明显萎缩性变化，与非痴呆对照组（ND）相比，其面积和体积均减小。此外，我们既没有发现星形胶质细胞丢失，也没有发现星形胶质细胞增殖或肥大（神经胶质增生）。与经典的星形胶质细胞增生假说相反，我们的结果显示出高度显著的星形胶质细胞萎缩，这可能对 AD 病理过程具有重要意义，是 SAD 和 FAD 中记忆和认知改变的基础和关键。
