Distl Roland, Treiber-Held Stephanie, Albert Frank, Meske Volker, Harzer Klaus, Ohm Thomas G
Institut für Anatomie, Charité, Humboldt Universität, Berlin, Germany.
J Pathol. 2003 May;200(1):104-11. doi: 10.1002/path.1320.
Niemann-Pick type C disease is an inherited neurovisceral storage disorder with intracellular accumulation of cholesterol. In affected brains, many ballooned neurons are seen. Considerable nerve cell loss of unknown pathogenesis leads to neurological deterioration and dementia. Chemical examination of brains has failed to demonstrate increased levels of cholesterol. Using filipin fluorometry of neuronal cells in tissue slices, we found massive accumulation of cholesterol in neurons in four out of five human Niemann-Pick type C cases including adult patients. Neurofibrillary tangles composed of aggregates of the otherwise highly soluble protein tau were present in three Niemann-Pick type C cases and were also immunologically identical to those associated with Alzheimer's disease. However, only a thin slab of spinal cord or a tiny piece of isocortex was available for examination in the two cases without tangles. In a further semi-quantitative analysis of 576 neurons, we determined higher cholesterol content in tangle-bearing neurons than in adjacent tangle-free neurons. The association of cholesterol accumulation with neurofibrillary degeneration in Niemann-Pick type C disease and Alzheimer's disease awakens interest in the role of impaired cholesterol metabolism in the development of neurofibrillary tangles in both diseases.
尼曼-匹克C型病是一种遗传性神经内脏贮积病，伴有细胞内胆固醇蓄积。在受影响的大脑中，可见许多气球样神经元。病因不明的大量神经细胞丢失导致神经功能恶化和痴呆。对大脑进行化学检测未能证明胆固醇水平升高。通过对组织切片中的神经元细胞进行荧光素染色荧光测定法，我们发现在包括成年患者在内的五例人类尼曼-匹克C型病病例中，有四例的神经元中存在大量胆固醇蓄积。在三例尼曼-匹克C型病病例中存在由原本高度可溶的蛋白质tau聚集形成的神经原纤维缠结，并且在免疫方面也与阿尔茨海默病相关的神经原纤维缠结相同。然而，在另外两例没有缠结的病例中，仅获得了一小片脊髓或一小块大脑皮质用于检查。在对576个神经元进行的进一步半定量分析中，我们确定有神经原纤维缠结的神经元中的胆固醇含量高于相邻的无缠结神经元。尼曼-匹克C型病和阿尔茨海默病中胆固醇蓄积与神经原纤维变性之间的关联引发了人们对胆固醇代谢受损在这两种疾病中神经原纤维缠结形成过程中所起作用的兴趣。
