Wegiel J, Wang K C, Tarnawski M, Lach B
Department of Pathological Neurobiology, New York State Institute for Basic Research in Developmental Disabilities, Staten Island 10314, USA.
Acta Neuropathol. 2000 Oct;100(4):356-64. doi: 10.1007/s004010000199.
Ultrastructural three-dimensional reconstruction of human classical plaques in different stages of development shows that microglial cells are the major factor driving plaque formation by fibrillar amyloid-beta (Abeta) deposition. The amount of fibrillar Abeta released by microglial cells and the area of direct contact between amyloid and neuron determine the extent of dystrophic changes in neuronal processes and synapses. The volume of hypertrophic astrocytic processes separating fibrillar amyloid from neuron is a measure of the protective activation of astrocytes. On the bases of the volume of amyloid star, microglial cells, dystrophic neurites, and hypertrophic astrocytic processes, and spatial relationships between plaque components, three stages in classical plaque development have been distinguished: early, mature, and late. In early plaque, the leading pathology is fibrillar Abeta deposition by microglial cells with amyloid star formation. The mature plaque is characterized by a balance between amyloid production, neuronal dystrophy, and astrocyte hypertrophy. In late classical plaque, microglial cells retract and expose neuropil on direct contact with amyloid star, enhancing both dystrophic changes in neurons and hypertrophic changes in astrocytes. In late plaques, activation of astrocytes predominates. They degrade amyloid star and peripheral amyloid wisps. The effect of these changes is classical plaque degradation to fibrillar primitive and finally to nonfibrillar, diffuse-like plaques.
对处于不同发育阶段的人类典型斑块进行超微结构三维重建显示，小胶质细胞是通过纤维状淀粉样β蛋白（Aβ）沉积驱动斑块形成的主要因素。小胶质细胞释放的纤维状Aβ的量以及淀粉样蛋白与神经元之间的直接接触面积决定了神经元突起和突触营养不良性变化的程度。将纤维状淀粉样蛋白与神经元分隔开的肥大星形胶质细胞突起的体积是星形胶质细胞保护性激活的一个指标。根据淀粉样蛋白星、小胶质细胞、营养不良性神经突和肥大星形胶质细胞突起的体积以及斑块成分之间的空间关系，区分出了典型斑块发育的三个阶段：早期、成熟和晚期。在早期斑块中，主要病理变化是小胶质细胞沉积纤维状Aβ并形成淀粉样蛋白星。成熟斑块的特征是淀粉样蛋白生成、神经元营养不良和星形胶质细胞肥大之间的平衡。在晚期典型斑块中，小胶质细胞退缩，使神经纤维网直接与淀粉样蛋白星接触，从而加剧神经元的营养不良性变化和星形胶质细胞的肥大性变化。在晚期斑块中，星形胶质细胞的激活占主导。它们降解淀粉样蛋白星和周边的淀粉样蛋白细丝。这些变化的结果是典型斑块降解为纤维状原始斑块，最终降解为非纤维状、弥漫样斑块。
