Departments of Pathology, Case Western Reserve University, School of Medicine, Cleveland, OH, 44106, USA.
Department of Pathology, 4th floor, room 402C, Case Western Reserve University, 2085 Adelbert Road, Cleveland, OH, 44106, USA.
Acta Neuropathol Commun. 2018 Jan 8;6(1):5. doi: 10.1186/s40478-017-0503-z.
The presence of pathology related to the deposition of amyloid-β (Aβ) has been recently reported in iatrogenic Creutzfeldt-Jakob disease (iCJD) acquired from inoculation of growth hormone (GH) extracted from human cadaveric pituitary gland or use of cadaveric dura mater (DM) grafts.To investigate this phenomenon further, a cohort of 27 iCJD cases - 21 with adequate number of histopathological sections - originating from Australia, France, Italy, and the Unites States, were examined by immunohistochemistry, amyloid staining, and Western blot analysis of the scrapie prion protein (PrP), and compared with age-group matched cases of sporadic CJD (sCJD), Alzheimer disease (AD) or free of neurodegenerative diseases (non-ND).Cases of iCJD and sCJD shared similar profiles of proteinase K-resistant PrP with the exception of iCJD harboring the "MMi" phenotype. Cerebral amyloid angiopathy (CAA), either associated with, or free of, Thioflavin S-positive amyloid core plaques (CP), was observed in 52% of 21 cases of iCJD, which comprised 37.5% and 61.5% of the cases of GH- and DM-iCJD, respectively. If only cases younger than 54 years were considered, Aβ pathology affected 41%, 2% and 0% of iCJD, sCJD and non-ND, respectively. Despite the patients' younger age CAA was more severe in iCJD than sCJD, while Aβ diffuse plaques, in absence of Aβ CP, populated one third of sCJD. Aβ pathology was by far most severe in AD. Tau pathology was scanty in iCJD and sCJD.In conclusion, (i) despite the divergences in the use of cadaveric GH and DM products, our cases combined with previous studies showed remarkably similar iCJD and Aβ phenotypes indicating that the occurrence of Aβ pathology in iCJD is a widespread phenomenon, (ii) CAA emerges as the hallmark of the Aβ phenotype in iCJD since it is observed in nearly 90% of all iCJD with Aβ pathology reported to date including ours, and it is shared by GH- and DM-iCJD, (iii) although the contributions to Aβ pathology of other factors, including GH deficiency, cannot be discounted, our findings increase the mounting evidence that this pathology is acquired by a mechanism resembling that of prion diseases.
最近有报道称，在因接种从人体尸检垂体中提取的生长激素（GH）或使用尸检硬脑膜（DM）移植物而获得的医源性克雅氏病（iCJD）中存在与淀粉样β（Aβ）沉积相关的病理学变化。为了进一步研究这一现象，对来自澳大利亚、法国、意大利和美国的 27 例 iCJD 病例（其中 21 例有足够数量的组织病理学切片）进行了免疫组织化学、淀粉样蛋白染色和对瘙痒性朊病毒蛋白（PrP）的 Western blot 分析，并与年龄匹配的散发型克雅氏病（sCJD）、阿尔茨海默病（AD）或无神经退行性疾病（非-ND）病例进行了比较。除了 iCJD 携带“MMi”表型外，iCJD 和 sCJD 病例的蛋白酶 K 抗性 PrP 具有相似的蛋白谱。在 21 例 iCJD 病例中，有 52%观察到脑淀粉样血管病（CAA），无论是否伴有 Thioflavin S 阳性淀粉样核心斑块（CP），其中 GH-iCJD 和 DM-iCJD 的比例分别为 37.5%和 61.5%。如果仅考虑年龄小于 54 岁的病例，Aβ 病理学影响分别为 41%、2%和 0%的 iCJD、sCJD 和非-ND。尽管患者年龄较轻，但 iCJD 的 CAA 比 sCJD 更严重，而在没有 Aβ CP 的情况下，Aβ 弥漫性斑块占据了三分之一的 sCJD。AD 的 Aβ 病理学迄今为止最为严重。在 iCJD 和 sCJD 中，tau 病理学都很少见。总之，（i）尽管在使用尸检 GH 和 DM 产品方面存在差异，但我们的病例与以前的研究结合表明，iCJD 和 Aβ 表型非常相似，这表明 Aβ 病理学在 iCJD 中的发生是一种普遍现象，（ii）CAA 是 iCJD 中 Aβ 表型的标志，因为它出现在迄今为止报告的所有具有 Aβ 病理学的 iCJD 中，包括我们的病例，并且在 GH-iCJD 和 DM-iCJD 中都有，（iii）尽管不能排除包括 GH 缺乏在内的其他因素对 Aβ 病理学的贡献，但我们的发现增加了越来越多的证据表明，这种病理学是通过类似于朊病毒疾病的机制获得的。
