Academic Unit of Pathology, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, UK.
Neurobiol Aging. 2010 Apr;31(4):578-90. doi: 10.1016/j.neurobiolaging.2008.05.015. Epub 2008 Jun 30.
Astrocyte pathology occurs in association with Alzheimer's disease (AD) and in brain ageing, but is poorly characterised. We sought to define the detailed cellular pathology of astrocytes, the extent of population variation and the relationship to Alzheimer-type changes in a population-based cohort. Three staining patterns were associated with GFAP and excitatory amino acid transporter 2 (EAAT2): minimal, moderate or extensive immunoreactivity. GFAP and EAAT2 expression were inversely related (p=0.015), with trends to increased expression of GFAP (p=0.019) and decreased expression of EAAT2 (p=ns) with increasing Braak stage. GFAP and EAAT2 correlated incompletely with beta-amyloid and tau immunoreactivity. However, gliosis increased with increasing burden of neuritic (p=0.011), but not diffuse (p=ns), plaques. Double-staining revealed distinct subsets of astrocytes; GFAP(+)EAAT(-), GFAP(-)EAAT(+), or GFAP(+)EAAT(+). In contrast to the variation in GFAP and EAAT2, levels of EAAT1 and S100B showed consistent staining patterns. Alzheimer-type pathology only partially explains the variation in gliosis and astrocyte functional markers, suggesting that other factors contribute to the population variance in astrocyte pathology.
星形胶质细胞病理学与阿尔茨海默病（AD）和脑老化有关，但特征描述较差。我们试图在基于人群的队列中定义星形胶质细胞的详细细胞病理学、群体变异程度以及与阿尔茨海默病样变化的关系。三种染色模式与 GFAP 和兴奋性氨基酸转运体 2（EAAT2）相关：最小、中度或广泛的免疫反应性。GFAP 和 EAAT2 的表达呈负相关（p=0.015），随着 Braak 阶段的增加，GFAP 的表达呈增加趋势（p=0.019），而 EAAT2 的表达呈减少趋势（p=ns）。GFAP 和 EAAT2 与β-淀粉样蛋白和 tau 免疫反应性不完全相关。然而，神经原纤维（p=0.011）而非弥漫性（p=ns）斑块的负担增加与神经胶质增生增加相关。双重染色显示星形胶质细胞的不同亚群；GFAP(+)EAAT(-)、GFAP(-)EAAT(+)或 GFAP(+)EAAT(+)。与 GFAP 和 EAAT2 的变化相反，EAAT1 和 S100B 的水平显示出一致的染色模式。阿尔茨海默病样病理学仅部分解释了神经胶质增生和星形胶质细胞功能标志物的变化，表明其他因素导致了星形胶质细胞病理学的人群变异。
