Leveugle B, Spik G, Perl D P, Bouras C, Fillit H M, Hof P R
Department of Geriatrics and Adult Development, Mount Sinai School of Medicine, New York, NY 10029.
Brain Res. 1994 Jul 4;650(1):20-31. doi: 10.1016/0006-8993(94)90202-x.
Lactotransferrin is a glycoprotein that specifically binds and transports iron. This protein is also believed to transport other metals such as aluminum. Several lines of evidence indicate that iron and aluminum are involved in the pathogenesis of many dementing diseases. In this context, the analysis of the iron-binding protein distribution in the brains of patients affected by neurodegenerative disorders is of particular interest. In the present study, the distribution of lactotransferrin was analyzed by immunohistochemistry in the cerebral cortex from patients presenting with Alzheimer's disease, Down syndrome, amyotrophic lateral sclerosis/parkinsonism-dementia complex of Guam, sporadic amyotrophic lateral sclerosis, or Pick's disease. The results show that lactotransferrin accumulates in the characteristic lesions of the different pathologic conditions investigated. For instance, in Alzheimer's disease and Guamanian cases, a subpopulation of neurofibrillary tangles was intensely labeled in the hippocampal formation and inferior temporal cortex. Senile plaques and Pick bodies were also consistently labeled. These staining patterns were comparable to those obtained with antibodies to the microtubule-associated protein tau and the amyloid beta A4 protein, although generally fewer neurofibrillary tangles were positive for lactotransferrin than for tau protein. Neuronal cytoplasmic staining with lactotransferrin antibodies, was observed in a subpopulation of pyramidal neurons in normal aging, and was more pronounced in Alzheimer's disease, Guamanian cases, Pick's disease, and particularly in Down syndrome. Lactotransferrin was also strongly associated with Betz cells and other motoneurons in the primary motor cortex of control, Alzheimer's disease, Down syndrome, Guamanian and Pick's disease cases. These same lactotransferrin-immunoreactive motoneurons were severely affected in the cases with amyotrophic lateral sclerosis. It is possible that in these neurodegenerative disorders affected neurons either take up or synthesize lactotransferrin to an abnormally elevated rate. An excessive accumulation of lactotransferrin, as well as transported iron and aluminum, may lead to a cytotoxic effect resulting in the formation of intracellular lesions and neuronal death.
乳铁传递蛋白是一种能特异性结合并转运铁的糖蛋白。该蛋白也被认为可转运其他金属，如铝。有几条证据表明铁和铝参与了许多痴呆疾病的发病机制。在此背景下，分析神经退行性疾病患者大脑中铁结合蛋白的分布情况尤为重要。在本研究中，通过免疫组织化学方法分析了患有阿尔茨海默病、唐氏综合征、关岛肌萎缩侧索硬化症/帕金森病 - 痴呆综合征、散发性肌萎缩侧索硬化症或皮克病患者大脑皮质中乳铁传递蛋白的分布。结果显示，乳铁传递蛋白在所研究的不同病理状况的特征性病变中蓄积。例如，在阿尔茨海默病和关岛病例中，海马结构和颞下回皮质中的一部分神经原纤维缠结被强烈标记。老年斑和皮克小体也一直被标记。这些染色模式与用微管相关蛋白tau和淀粉样β A4蛋白抗体获得的模式相似，尽管通常乳铁传递蛋白阳性的神经原纤维缠结比tau蛋白阳性的要少。在正常衰老过程中，乳铁传递蛋白抗体在一部分锥体神经元的细胞质中染色，在阿尔茨海默病、关岛病例、皮克病中更明显，在唐氏综合征中尤为显著。在对照、阿尔茨海默病、唐氏综合征、关岛和皮克病病例的初级运动皮质中，乳铁传递蛋白也与贝茨细胞和其他运动神经元密切相关。在肌萎缩侧索硬化症病例中，这些相同的乳铁传递蛋白免疫反应性运动神经元受到严重影响。在这些神经退行性疾病中，受影响的神经元可能以异常升高的速率摄取或合成乳铁传递蛋白。乳铁传递蛋白以及所转运的铁和铝的过度蓄积可能导致细胞毒性作用，从而导致细胞内病变的形成和神经元死亡。
