Alzheimer's disease neuropathological change three decades after iatrogenic amyloid-β transmission.
Alzheimer's disease neuropathological change three decades after iatrogenic amyloid-β transmission.
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DOI：
10.1007/s00401-021-02326-y
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发表时间：
2021-07
影响因子：
12.7
通讯作者：
Brandner S
中科院分区：
文献类型：
--
作者：
Jaunmuktane Z;Banerjee G;Paine S;Parry-Jones A;Rudge P;Grieve J;Toma AK;Farmer SF;Mead S;Houlden H;Werring DJ;Brandner S
在患有和不患有医源性克雅氏病（iCJD）的患者的脑活检或尸检组织中显示了β淀粉样蛋白（A β）病理的人（医源性）传播[1，5 - 18，20 - 22]，并且在含有人尸体衍生生长激素（hGH）的存档小瓶中检测到了这些A β种子[7，19]。虽然在这些hGH小瓶中也发现了tau种子[7，19]，但迄今为止，在iCJD、医源性传播的A β病理或两者兼有的患者中未观察到实质性tau病理。在此，我们发现，医源性A β病理患者在潜伏期超过30年后，可出现与阿尔茨海默病患者相似的显著tau病理。病例1：一名46岁男性，有12个月的认知功能下降、进行性共济失调和肌阵挛病史。他在4岁时切除了髓母细胞瘤，但不知道是否使用了硬脑膜补片。病人有学习困难，因为他的肿瘤放射化疗，但几个月后，在44岁的尾状核出血，他逐渐发展认知能力下降。右额叶脑活检显示软脑膜和皮质A β血管病（CAA），实质淀粉样蛋白-β伴弥漫性沉积和斑块，中心淀粉样蛋白核心（图1 a），以及tau病变，形成神经纤维丝、前缠结、缠结和神经炎斑块的网状结构（图1 b-e）。病人在47岁时去世。APOE
Human (iatrogenic) transmission of amyloid-β (Aβ) pathology has been shown in brain biopsy or autopsy tissues in patients with and without iatrogenic Creutzfeldt–Jakob disease (iCJD)[1, 5–18, 20–22] and these Aβ seeds have been detected in the archival vials containing human cadaverderived growth hormone (hcGH)[7, 19]. Whilst tau seeds were also found in these hcGH vials [7, 19], to date, no substantial tau pathology has been observed in patients with iCJD, iatrogenically transmitted Aβ pathology or both. Here we show that a significant tau pathology, similar to that seen in patients with Alzheimer’s disease, can develop in patients with iatrogenic Aβ pathology after incubation periods exceeding 3 decades.Case 1: a 46-year-old male presented with a 12-month history of cognitive decline, progressive ataxia and myoclonus. He had a medulloblastoma resected at the age of 4 years, but it is not known if a dura patch was used. The patient had learning difficulties since the radio-chemotherapy of his tumour but several months after a caudate nucleus haemorrhage at age 44, he developed gradual cognitive decline. A right frontal brain biopsy showed leptomeningeal and cortical Aβ angiopathy (CAA), parenchymal amyloid-β with diffuse deposits and plaques with central amyloid cores (Fig. 1 a), and a tauopathy forming a meshwork of neuropil threads, pre-tangles, tangles and neuritic plaques (Fig. 1 b–e). The patient died at the age of 47. APOE
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影响因子：
12.7
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
通讯作者：
Ironside JW
影响因子：
11.2
作者：
Banerjee, Gargi;Adams, Matthew E.;Werring, David J.
通讯作者：
Werring, David J.
DOI：
10.1097/nen.0b013e318232a379
发表时间：
2011-11-01
影响因子：
3.2
作者：
Braak, Heiko;Thal, Dietmar R.;Del Tredici, Kelly
通讯作者：
Del Tredici, Kelly
影响因子：
2.3
作者：
Iwasaki, Yasushi;Imamura, Kazuhiro;Yoshida, Mari
通讯作者：
Yoshida, Mari
影响因子：
11.4
作者：
Brooke, FJ;Boyd, A;Collins, SJ
通讯作者：
Collins, SJ