Nakamura S, Ono F, Hamano M, Odagiri K, Kubo M, Komatsuzaki K, Terao K, Shinagawa M, Takahashi K, Yoshikawa Y
Department of Veterinary Pathology, Nippon Veterinary and Animal Science University, Tokyo, Japan.
Acta Neuropathol. 2000 Oct;100(4):365-70. doi: 10.1007/s004010000200.
The interaction of various amyloid precursors and apolipoprotein E (apoE) is important for Congophilic amyloid formation. As for cerebral amyloidoses, although the correlation between amyloid beta protein (Abeta) and apoE in Alzheimer's disease (AD) has been clarified, the interaction of prion protein isoform (PrPsc) and apoE in several types of prion diseases (PDs) has not been examined in detail. ApoE colocalization has been confirmed in Congophilic PrPsc plaques, but to clarify the participation of apoE in the early stage of PDs, apoE deposition in immature lesions without Congophilic amyloid in PDs needs to be examined. In the present study two squirrel monkeys were inoculated with mouse PrPsc derived from sheep scrapie, and showed signs of severe spongiform degeneration. These lesions were immunohistochemically characterized as patchy perivacuolar and diffuse synaptic lesions without Congophilic amyloid. The central portion of the assemblies involving a few patchy perivacuolar lesions was detected by methenamine silver staining and appeared as a plaque-like lesion. ApoE was colocalized in all the plaque-like lesions and in half of the patchy perivacuolar lesions, but not in any diffuse synaptic lesions. These immunohistochemical characteristics indicated that apoE colocalization occurred in moderate mature lesions in PDs, and apoE might play an important role in the aggregation of PrPsc after a conformational change from cellular PrP isoform to PrPsc.
各种淀粉样前体蛋白与载脂蛋白E（apoE）的相互作用对于嗜刚果红性淀粉样蛋白的形成很重要。至于脑淀粉样变性，尽管阿尔茨海默病（AD）中淀粉样β蛋白（Aβ）与apoE之间的相关性已得到阐明，但几种朊病毒疾病（PDs）中朊病毒蛋白异构体（PrPsc）与apoE的相互作用尚未得到详细研究。在嗜刚果红性PrPsc斑块中已证实apoE共定位，但为了阐明apoE在PDs早期阶段的参与情况，需要检查PDs中无嗜刚果红性淀粉样蛋白的未成熟病变中的apoE沉积情况。在本研究中，给两只松鼠猴接种了源自绵羊瘙痒病的小鼠PrPsc，它们出现了严重海绵状变性的迹象。这些病变经免疫组织化学鉴定为散在的空泡周围和弥漫性突触病变，无嗜刚果红性淀粉样蛋白。通过六胺银染色检测到涉及一些散在空泡周围病变的聚集物中央部分，呈现为斑块样病变。ApoE在所有斑块样病变和一半散在空泡周围病变中共定位，但在任何弥漫性突触病变中均未共定位。这些免疫组织化学特征表明，apoE共定位发生在PDs的中度成熟病变中，并且apoE可能在PrPsc从细胞PrP异构体构象转变为PrPsc后的聚集过程中起重要作用。
