Stalder M, Deller T, Staufenbiel M, Jucker M
Department of Neuropathology, Institute of Pathology, University of Basel, Basel, Switzerland.
Neurobiol Aging. 2001 May-Jun;22(3):427-34. doi: 10.1016/s0197-4580(01)00209-3.
Microglia cells are closely associated with compact amyloid plaques in Alzheimer's disease (AD) brains. Although activated microglia seem to play a central role in the pathogenesis of AD, mechanisms of microglial activation by beta-amyloid as well as the nature of interaction between amyloid and microglia remain poorly understood. We previously reported a close morphological association between activated microglia and congophilic amyloid plaques in the brains of APP23 transgenic mice at both the light and electron microscopic levels [25]. In the present study, we have further examined the structural relationship between microglia and amyloid deposits by using postembedding immunogold labeling, serial ultrathin sectioning, and 3-dimensional reconstruction. Although bundles of immunogold-labeled amyloid fibrils were completely engulfed by microglial cytoplasm on single sections, serial ultrathin sectioning and three-dimensional reconstruction revealed that these amyloid fibrils are connected to extracellular amyloid deposits. These data demonstrate that extracellular amyloid fibrils form a myriad of finger-like channels with the widely branched microglial cytoplasm. We conclude that in APP23 mice a role of microglia in amyloid phagocytosis and intracellular production of amyloid is unlikely.
在阿尔茨海默病（AD）患者的大脑中，小胶质细胞与致密的淀粉样斑块密切相关。尽管活化的小胶质细胞似乎在AD的发病机制中起核心作用，但β-淀粉样蛋白激活小胶质细胞的机制以及淀粉样蛋白与小胶质细胞之间相互作用的本质仍知之甚少。我们之前报道过，在光镜和电镜水平上，APP23转基因小鼠大脑中活化的小胶质细胞与嗜刚果红淀粉样斑块之间存在密切的形态学关联[25]。在本研究中，我们通过包埋后免疫金标记、连续超薄切片和三维重建，进一步研究了小胶质细胞与淀粉样沉积物之间的结构关系。尽管在单张切片上，免疫金标记的淀粉样纤维束被小胶质细胞的细胞质完全吞噬，但连续超薄切片和三维重建显示，这些淀粉样纤维与细胞外淀粉样沉积物相连。这些数据表明，细胞外淀粉样纤维与广泛分支的小胶质细胞细胞质形成了无数指状通道。我们得出结论，在APP23小鼠中，小胶质细胞在淀粉样蛋白吞噬和细胞内淀粉样蛋白产生中不太可能起作用。
