Hof P R, Nimchinsky E A, Buée-Scherrer V, Buée L, Nasrallah J, Hottinger A F, Purohit D P, Loerzel A J, Steele J C, Delacourte A
Department of Neurobiology, Mount Sinai School of Medicine, New York, NY 10029.
Acta Neuropathol. 1994;88(5):397-404. doi: 10.1007/BF00389490.
Amyotrophic lateral sclerosis/parkinsonism-dementia complex (lytico-bodig) is a chronic neurodegenerative disorder with high prevalence among the native Chamorro population of Guam. Neuropathological, biochemical, and immunohistochemical analyses were performed on a relatively large series of Guamanian cases and compared to Alzheimer's disease cases. Thioflavin S and antibodies to amyloid beta A4 and tau proteins were used for analysis of pathological changes, and antibodies to the calcium-binding proteins parvalbumin and calretinin, and to a nonphosphorylated epitope on neurofilament protein to study select neuronal populations. A differential distribution of neurofibrillary tangles was observed in the neocortex of Guamanian cases compared to Alzheimer's disease cases, with much higher lesion counts in supragranular than in infragranular layers. Also, Guamanian cases with predominant parkinsonism had generally higher neurofibrillary tangle densities than cases with predominant amyotrophic lateral sclerosis. In addition, there was a certain degree of heterogeneity, qualitatively and quantitatively, in the biochemical distribution of tau proteins among Guamanian and Alzheimer's disease cases as revealed by Western blot analysis. Previous studies have suggested that the clinical symptomatology observed in patients suffering from Alzheimer's disease is related to the dramatic loss of specific corticocortically projecting neurons in the neocortex. Interestingly, a subset of neurofilament-rich pyramidal neurons known to be dramatically affected in Alzheimer's disease appears to be resistant in lytico-bodig. Finally, as in Alzheimer's disease, calcium-binding protein-containing interneurons are not affected. These data suggest that the set of projection neurons affected in Guamanian cases may not correspond to those involved in Alzheimer's disease, and that both disorders are characterized by specific patterns of neuronal vulnerability.
肌萎缩侧索硬化症/帕金森病-痴呆综合征（lytico-bodig）是一种慢性神经退行性疾病，在关岛的查莫罗原住民中具有较高的患病率。对一系列相对较多的关岛病例进行了神经病理学、生物化学和免疫组织化学分析，并与阿尔茨海默病病例进行了比较。使用硫黄素S以及针对淀粉样β蛋白A4和tau蛋白的抗体来分析病理变化，使用针对钙结合蛋白小白蛋白和钙视网膜蛋白以及神经丝蛋白上的非磷酸化表位的抗体来研究特定的神经元群体。与阿尔茨海默病病例相比，在关岛病例的新皮质中观察到神经原纤维缠结的分布存在差异，颗粒上层的病变数量远高于颗粒下层。此外，以帕金森症状为主的关岛病例的神经原纤维缠结密度通常高于以肌萎缩侧索硬化为主的病例。另外，蛋白质印迹分析显示，关岛病例和阿尔茨海默病病例中tau蛋白的生化分布在定性和定量上都存在一定程度的异质性。先前的研究表明，阿尔茨海默病患者观察到的临床症状与新皮质中特定的皮质-皮质投射神经元的显著丧失有关。有趣的是，已知在阿尔茨海默病中受到显著影响的富含神经丝的锥体神经元的一个亚群在lytico-bodig中似乎具有抗性。最后，与阿尔茨海默病一样，含有钙结合蛋白的中间神经元未受影响。这些数据表明，在关岛病例中受影响的投射神经元组可能与阿尔茨海默病中涉及的神经元组不同，并且这两种疾病都具有特定的神经元易损模式。
