Amyloid-β accumulation in the CNS in human growth hormone recipients in the UK.
Amyloid-β accumulation in the CNS in human growth hormone recipients in the UK.
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DOI：
10.1007/s00401-017-1703-0
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发表时间：
2017-08
影响因子：
12.7
通讯作者：
Ironside JW
中科院分区：
文献类型：
--
作者：
Ritchie DL;Adlard P;Peden AH;Lowrie S;Le Grice M;Burns K;Jackson RJ;Yull H;Keogh MJ;Wei W;Chinnery PF;Head MW;Ironside JW
克雅氏病（CJD）的人际传播已经通过医疗程序发生，导致医源性CJD （iCJD）。iCJD最常见的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。作为迄今为止收集的英国hGH-iCJD病例（35例）的最大队列的综合组织分析的一部分，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18/33例hGH- icjd患者的大脑和脑血管中与阿尔茨海默病（AD）相关的淀粉样蛋白β (Aβ)的积累，并且首次在5/12例死于CJD以外原因的hGH受体中。在死于散发性和变异型CJD的年龄匹配患者中，Aβ积累明显不那么普遍。这些结果与假设一致，即a β可以在垂体中积累，存在于接种的hGH制剂中，并且在大约50%的hGH受体中具有播种效应，产生ad样神经病理和脑淀粉样血管病（CAA），无论是否发生CJD神经病理。这些发现表明，在人脑中没有异常朊蛋白的情况下，Aβ的播散可以独立发生。我们的研究结果为Aβ的朊病毒样播种特性提供了进一步的证据，并为AD和CAA医源性传播的可能性提供了见解。本文的在线版本（doi:10.1007/s00401-017-1703-0）包含补充资料，仅供授权用户使用。
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. The online version of this article (doi:10.1007/s00401-017-1703-0) contains supplementary material, which is available to authorized users.
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来自1,092个人基因组的遗传变异的综合图。
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
7
作者：
Keogh MJ;Wei W;Wilson I;Coxhead J;Ryan S;Rollinson S;Griffin H;Kurzawa-Akanbi M;Santibanez-Koref M;Talbot K;Turner MR;McKenzie CA;Troakes C;Attems J;Smith C;Al Sarraj S;Morris CM;Ansorge O;Pickering-Brown S;Ironside JW;Chinnery PF
通讯作者：
Chinnery PF
影响因子：
2.3
作者：
Homma, Taku;Mochizuki, Yoko;Mizutani, Toshio
通讯作者：
Mizutani, Toshio
影响因子：
11.8
作者：
Brown P;Brandel JP;Sato T;Nakamura Y;MacKenzie J;Will RG;Ladogana A;Pocchiari M;Leschek EW;Schonberger LB
通讯作者：
Schonberger LB
影响因子：
39.2
作者：
Edgren, Gustaf;Hjalgrim, Henrik;Nyren, Olof
通讯作者：
Nyren, Olof