Liberski P P, Budka H
Institute of Neurology, University of Vienna, and Austrian Reference Center for Human Prion Diseases (ORPE).
Acta Neuropathol. 1999 Apr;97(4):329-34. doi: 10.1007/s004010050995.
Neuroaxonal pathology has met little attention in transmissible spongiform encephalopathies. In brains of a series of 39 consecutive Creutzfeldt-Jakob disease (CJD) cases, we detected numerous abnormal neurites that labeled for neurofilament proteins (NFP) by immunocytochemistry. Three types of abnormally NFP-accumulating structures were more prominently observed in CJD brains than in age-matched control brains: 1. Neurons with NFP in their somata were seen in 29 CJD cases (74%), some appearing distended with eccentrically placed nuclei and homogenously stained cytoplasm. 2. Neuritic distensions (neuritic swellings, dystrophic neurites) were observed mainly in the white matter but also at the junction between gray and white matter. In some axons many such swellings could be traced along the visible part of the axonal segment. 3. Axonal spheroids were observed mainly in the medulla, predominantly but not exclusively in posterior nuclei, and were more numerous than in age-matched control brains. Several neurons, axons and spheroids demonstrated immunoreactivity for amyloid precursor protein. Their number was much smaller, however, than that of NFP-immunoreactive structures and varied from one or two immunopositive neurites per section to small clusters of beaded or spiral axons. Focal expression of apolipoprotein E in cells of microglial and astrocytic morphology was observed in areas with most pronounced axonal damage. We conclude that neuroaxonal pathology is a frequent and important part of brain lesioning in CJD, probably reflecting profound impairment of axonal transport.
神经轴突病理学在传染性海绵状脑病中很少受到关注。在连续的39例克雅氏病（CJD）患者的大脑中，我们通过免疫细胞化学检测到许多标记神经丝蛋白（NFP）的异常神经突。与年龄匹配的对照大脑相比，在CJD大脑中更明显地观察到三种类型的异常NFP积聚结构：1. 29例CJD病例（74%）中可见胞体中有NFP的神经元，一些神经元看起来肿胀，核偏心，细胞质均匀染色。2. 神经突扩张（神经突肿胀、营养不良性神经突）主要见于白质，但也见于灰质和白质交界处。在一些轴突中，许多这样的肿胀可以沿着轴突段的可见部分追踪到。3. 轴突球状体主要见于延髓，主要但不仅限于后核，且比年龄匹配的对照大脑中更多。一些神经元、轴突和球状体对淀粉样前体蛋白呈免疫反应性。然而，它们的数量比NFP免疫反应性结构少得多，每切片从一两个免疫阳性神经突到小串珠状或螺旋状轴突不等。在轴突损伤最明显的区域观察到小胶质细胞和星形胶质细胞形态的细胞中载脂蛋白E的局灶性表达。我们得出结论，神经轴突病理学是CJD脑损伤的常见且重要组成部分，可能反映了轴突运输的严重受损。
