Wood Oliver W G, Yeung Jason H Y, Palpagama Thulani H, Turner Clinton, Waldvogel Henry J, Faull Richard L M, Kwakowsky Andrea
Centre for Brain Research and Department of Anatomy and Medical Imaging, Faculty of Medical and Health Sciences, University of Auckland, New Zealand.
Department of Anatomical Pathology, LabPLUS, Auckland City Hospital, New Zealand.
Neuroscience. 2025 Feb 6;566:87-96. doi: 10.1016/j.neuroscience.2024.12.027. Epub 2024 Dec 16.
Alzheimer's disease (AD) is a growing health problem worldwide, particularly in the developed world due to an ageing population. Glutamate excitotoxicity plays a major role in the pathophysiology of AD, and glutamate re-uptake is controlled by excitatory amino acid transporters (EAATs). The EAAT2 isoform is the predominant transporter involved in glutamate reuptake, therefore EAAT1 has not been the focus of AD research. We investigated the layer-specific expression of EAAT1 in human medial temporal lobe regions such as the hippocampus, subiculum, entorhinal cortex and superior temporal gyrus, using fluorescent immunohistochemistry and laser scanning confocal microscopy in human post-mortem tissue. We observed low EAAT1 immunoreactivity in control cases, but upregulated labeling in AD across several brain regions of the medial temporal lobe. Significantly higher integrated density in AD cases was observed in the str. oriens and str. radiatum of the CA2 region, the str. pyramidale of CA3, and the str. moleculare and str. granulosum of the DG. Labeling of EAAT1 appeared astrocytic in nature, showing close association with astrocytic processes in AD cases. We also report that a higher EAAT1 density was positively correlated with the age of AD cases, but this relationship was not observed in control cases. Overall, our results indicate an upregulation of EAAT1 across several hippocampal subregions and layers in AD cases, indicating a potential physiological role for this transporter that needs further investigation.
阿尔茨海默病（AD）在全球范围内是一个日益严重的健康问题，尤其是在发达国家，因为人口老龄化。谷氨酸兴奋性毒性在AD的病理生理学中起主要作用，谷氨酸再摄取由兴奋性氨基酸转运体（EAATs）控制。EAAT2亚型是参与谷氨酸再摄取的主要转运体，因此EAAT1一直不是AD研究的重点。我们使用荧光免疫组织化学和激光扫描共聚焦显微镜，在人类尸检组织中研究了EAAT1在人类内侧颞叶区域（如海马体、下托、内嗅皮质和颞上回）的层特异性表达。我们在对照病例中观察到EAAT1免疫反应性较低，但在AD患者的内侧颞叶多个脑区中标记上调。在AD病例中，CA2区的 Oriens层和辐射层、CA3的锥体层以及齿状回的分子层和颗粒层观察到显著更高的积分密度。EAAT1的标记在本质上似乎是星形细胞性的，在AD病例中显示与星形细胞过程密切相关。我们还报告说，较高的EAAT1密度与AD病例的年龄呈正相关，但在对照病例中未观察到这种关系。总体而言，我们的结果表明AD病例中多个海马亚区和层的EAAT1上调，表明该转运体具有潜在的生理作用，需要进一步研究。
