Mass General Institute for Neurodegenerative Disease, Massachusetts General Hospital, Massachusetts Alzheimer Disease Research Center, and Harvard Medical School, Charlestown, Massachusetts, USA.
J Neuropathol Exp Neurol. 2013 Jun;72(6):462-71. doi: 10.1097/NEN.0b013e3182933788.
Although it is clear that astrocytes and microglia cluster around dense-core amyloid plaques in Alzheimer disease (AD), whether they are primarily attracted to amyloid deposits or are just reacting to plaque-associated neuritic damage remains elusive. We postulate that astrocytes and microglia may differentially respond to fibrillar amyloid β. Therefore, we quantified the size distribution of dense-core thioflavin-S (ThioS)-positive plaques in the temporal neocortex of 40 AD patients and the microglial and astrocyte responses in their vicinity (≤50 μm) and performed correlations between both measures. As expected, both astrocytes and microglia were clearly spatially associated with ThioS-positive plaques (p = 0.0001, ≤50 μm vs. >50 μm from their edge), but their relationship to ThioS-positive plaque size differed: larger ThioS-positive plaques were associated with more surrounding activated microglia (p = 0.0026), but this effect was not observed with reactive astrocytes. Microglial response to dense-core plaques seems to be proportional to their size, which we postulate reflects a chemotactic effect of amyloid β. By contrast, plaque-associated astrocytic response does not correlate with plaque size and seems to parallel the behavior of plaque-associated neuritic damage.
虽然很明显星形胶质细胞和小胶质细胞聚集在阿尔茨海默病（AD）中的致密核心淀粉样斑块周围，但它们是主要被淀粉样沉积物吸引，还是只是对斑块相关的神经突损伤做出反应，这仍然难以捉摸。我们假设星形胶质细胞和小胶质细胞可能对纤维状淀粉样β有不同的反应。因此，我们定量分析了 40 例 AD 患者颞叶皮质中致密核心硫黄素-S（ThioS）阳性斑块的大小分布，以及其附近（≤50μm）的小胶质细胞和星形胶质细胞的反应，并对这两种测量方法进行了相关性分析。正如预期的那样，星形胶质细胞和小胶质细胞都明显与 ThioS 阳性斑块有空间关联（p=0.0001，≤50μm 与>50μm 相比），但它们与 ThioS 阳性斑块大小的关系不同：较大的 ThioS 阳性斑块与周围更多的激活小胶质细胞有关（p=0.0026），但这种效应在反应性星形胶质细胞中没有观察到。小胶质细胞对致密核心斑块的反应似乎与其大小成正比，我们推测这反映了淀粉样β的趋化作用。相比之下，斑块相关星形胶质细胞的反应与斑块大小无关，似乎与斑块相关的神经突损伤的行为平行。
