Masliah E, Mallory M, Hansen L, Alford M, DeTeresa R, Terry R
University of California, San Diego, School of Medicine, Department of Neurosciences, La Jolla.
Am J Pathol. 1993 Mar;142(3):871-82.
We studied axonal damage in Alzheimer's disease frontal cortex and hippocampus with a novel monoclonal antibody (SMI 312) against phosphorylated neurofilaments. This antibody immunolabeled, with great detail, the neuropil axonal network. In aged normal cases only a few pyramidal cell perikarya were immunostained. In Alzheimer's disease there was a two- to four-fold increase in neuronal SMI 312 immunolabeling, and neuropil neuritic processes were severely disrupted. Double-immunolabeling analysis showed that 88% of SMI 312-immunolabeled abnormal neuritic clusters were associated with amyloid, whereas the remaining 12% were not. Serial section analysis and 3-D reconstructions suggested that dystrophic neurites of classical plaques were derived from long axons. These abnormal neurites were also growth-associated protein 43 positive and occasionally tau positive. The present study supports the contention that a subpopulation of aberrantly sprouting axons in the neuritic plaque is derived from cortico-cortico fibers. This disruption of the neocortical association fibers and neuritic microcircuitry could underlie the cognitive impairment of Alzheimer's disease.
我们使用一种针对磷酸化神经丝的新型单克隆抗体（SMI 312）研究了阿尔茨海默病额叶皮质和海马中的轴突损伤。该抗体能非常详细地免疫标记神经毡轴突网络。在老年正常病例中，只有少数锥体细胞的胞体被免疫染色。在阿尔茨海默病中，神经元SMI 312免疫标记增加了两到四倍，并且神经毡神经突过程严重受损。双重免疫标记分析表明，88%的SMI 312免疫标记的异常神经突簇与淀粉样蛋白相关，而其余12%则不相关。连续切片分析和三维重建表明，经典斑块的营养不良性神经突源自长轴突。这些异常神经突生长相关蛋白43也呈阳性，偶尔tau也呈阳性。本研究支持这样的观点，即神经炎性斑块中异常发芽轴突的一个亚群源自皮质 - 皮质纤维。新皮质联合纤维和神经突微回路的这种破坏可能是阿尔茨海默病认知障碍的基础。
