National CJD Research & Surveillance Unit, Centre for Clinical Brain Sciences, Deanery of Clinical Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK.
UCL Great Ormond Street Institute of Child Health, 30 Guilford Street, London, WC1N 1EH, UK.
Acta Neuropathol. 2017 Aug;134(2):221-240. doi: 10.1007/s00401-017-1703-0. Epub 2017 Mar 27.
Human-to-human transmission of Creutzfeldt-Jakob disease (CJD) has occurred through medical procedures resulting in iatrogenic CJD (iCJD). One of the commonest causes of iCJD was the use of human pituitary-derived growth hormone (hGH) to treat primary or secondary growth hormone deficiency. As part of a comprehensive tissue-based analysis of the largest cohort yet collected (35 cases) of UK hGH-iCJD cases, we describe the clinicopathological phenotype of hGH-iCJD in the UK. In the 33/35 hGH-iCJD cases with sufficient paraffin-embedded tissue for full pathological examination, we report the accumulation of the amyloid beta (Aβ) protein associated with Alzheimer's disease (AD) in the brains and cerebral blood vessels in 18/33 hGH-iCJD patients and for the first time in 5/12 hGH recipients who died from causes other than CJD. Aβ accumulation was markedly less prevalent in age-matched patients who died from sporadic CJD and variant CJD. These results are consistent with the hypothesis that Aβ, which can accumulate in the pituitary gland, was present in the inoculated hGH preparations and had a seeding effect in the brains of around 50% of all hGH recipients, producing an AD-like neuropathology and cerebral amyloid angiopathy (CAA), regardless of whether CJD neuropathology had occurred. These findings indicate that Aβ seeding can occur independently and in the absence of the abnormal prion protein in the human brain. Our findings provide further evidence for the prion-like seeding properties of Aβ and give insights into the possibility of iatrogenic transmission of AD and CAA.
人类朊病毒病（CJD）可通过导致医源性 CJD（iCJD）的医疗程序在人与人之间传播。iCJD 的最常见原因之一是使用人垂体源性生长激素（hGH）治疗原发性或继发性生长激素缺乏症。作为对迄今为止收集的最大队列（35 例）英国 hGH-iCJD 病例进行的全面基于组织的分析的一部分，我们描述了英国 hGH-iCJD 的临床病理表型。在 33/35 例具有足够石蜡包埋组织进行全面病理检查的 hGH-iCJD 病例中，我们报告了与阿尔茨海默病（AD）相关的淀粉样蛋白β（Aβ）蛋白在 18/33 例 hGH-iCJD 患者的大脑和脑血管中的积累，并且首次在 5/12 例死于 CJD 以外原因的 hGH 接受者中发现。Aβ 积累在年龄匹配的死于散发性 CJD 和变异 CJD 的患者中明显较少见。这些结果与以下假设一致，即可以在垂体中积累的 Aβ 存在于接种的 hGH 制剂中，并在大约 50%的所有 hGH 接受者的大脑中产生种籽效应，产生类似于 AD 的神经病理学和脑淀粉样血管病（CAA），无论是否发生 CJD 神经病理学。这些发现表明，Aβ 种籽可以独立于大脑中的异常朊病毒蛋白发生。我们的发现为 Aβ 的类朊病毒样种籽特性提供了进一步的证据，并深入了解了医源性 AD 和 CAA 传播的可能性。
