Grundke-Iqbal I, Fleming J, Tung Y C, Lassmann H, Iqbal K, Joshi J G
New York State Institute for Basic Research in Developmental Disabilities, Staten Island 10314.
Acta Neuropathol. 1990;81(2):105-10. doi: 10.1007/BF00334497.
A strong immunoreactivity for ferritin was observed in the neuritic (senile) plaques in Alzheimer's disease hippocampus. The ferritin accumulation was almost exclusively associated with the microglia, which appeared to have proliferated greatly. These cells were also positive for HLA-DR, a putative marker for reactive microglia. In contrast, in the diffuse plaques, which were without neuritic pathology, the ferritin-stained microglia appeared to be normal. Microglia were seen frequently in contact with neurons undergoing neurofibrillary changes but only the tangles in the extracellular space were ferritin positive. No ferritin was detected, by Western blots, in paired helical filaments isolated from Alzheimer's disease brain, suggesting that ferritin was most likely weakly associated with and was not a constituent of these fibrils. No correlation between increased ferritin/microglia activity and blood-brain barrier leakage was detected. Ferritin, an iron-storage protein, might have a role in the formation of amyloid through the action of free radicals generated during the release of iron from the ferritin molecule. Alternatively, the ferritin/microglia system might be secondarily involved in the removal and processing of the amyloid.
在阿尔茨海默病海马体的神经炎性（老年）斑块中观察到铁蛋白有强烈的免疫反应性。铁蛋白积累几乎完全与小胶质细胞相关，这些小胶质细胞似乎大量增殖。这些细胞对HLA - DR也呈阳性，HLA - DR是反应性小胶质细胞的一种假定标志物。相比之下，在没有神经炎性病理改变的弥漫性斑块中，铁蛋白染色的小胶质细胞似乎是正常的。经常可见小胶质细胞与经历神经原纤维变化的神经元接触，但只有细胞外空间的缠结呈铁蛋白阳性。通过蛋白质免疫印迹法，在从阿尔茨海默病大脑分离出的双螺旋丝中未检测到铁蛋白，这表明铁蛋白很可能与这些纤维弱相关且不是其组成成分。未检测到铁蛋白/小胶质细胞活性增加与血脑屏障渗漏之间的相关性。铁蛋白是一种铁储存蛋白，可能通过铁蛋白分子中铁释放过程中产生的自由基作用在淀粉样蛋白形成中发挥作用。或者，铁蛋白/小胶质细胞系统可能继发参与淀粉样蛋白的清除和处理。
