Presence of tau pathology within foetal neural allografts in patients with Huntington's and Parkinson's disease
Presence of tau pathology within foetal neural allografts in patients with Huntington's and Parkinson's disease
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DOI：
10.1093/brain/awx255
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发表时间：
2017-11-01
期刊：
影响因子：
14.5
通讯作者：
Cicchetti, Francesca
中科院分区：
文献类型：
--
作者：
Cisbani, Giulia;Maxan, Alexander;Cicchetti, Francesca
细胞替代已被探索作为一种治疗策略，以修复患有亨廷顿病和帕金森病的患者的大脑。在这种情况下，对健康移植组织的尸检评估揭示了亨廷顿或帕金森样病理学的发展，包括突变的亨廷顿蛋白聚集体和路易体。一个悬而未决的问题仍然是，tau蛋白病理学是否也可以在接受胎儿神经同种异体移植的亨廷顿病和帕金森病患者中观察到。这是通过对两名亨廷顿病患者移植组织进行免疫组织化学/免疫荧光染色来解决的，这两名患者在移植后9年和12年进行尸检，两名帕金森病患者在移植后18个月和16年进行尸检。我们发现，在两种类型的移植患者中，移植物也含有tau病理。在两名患有亨廷顿病的患者中，移植组织显示存在过度磷酸化的tau [AT 8（磷酸化tau Ser 202和Thr 205）和CP 13（pSer 202）免疫组织化学染色]病理性包涵体、神经纤维缠结和神经纤维丝。在帕金森病患者中，移植组织的特征在于过度磷酸化的tau（AT 8;免疫荧光染色）病理性内含物，神经纤维缠结和神经纤维丝，但仅在移植后16年进行尸检的患者中。在所有研究病例的皮质和纹状体中观察到丰富的tau相关病理学。虽然移植的亨廷顿病患者的纹状体显示出等量的tau的3-重复和4-重复同种型，但通过蛋白质印迹，移植的组织显示出升高的4-重复同种型。这表明移植物可能已经从宿主大脑中获得了tau病理学，尽管另一种可能性是这是由于加速老化。这一发现不仅增加了最近的报道，即tau病理是这些神经退行性疾病的一个特征，而且tau病理可以在移植到患有两种不同神经退行性疾病的患者大脑中的健康神经组织中表现出来。
Cell replacement has been explored as a therapeutic strategy to repair the brain in patients with Huntington's and Parkinson's disease. Post-mortem evaluations of healthy grafted tissue in such cases have revealed the development of Huntington- or Parkinson-like pathology including mutant huntingtin aggregates and Lewy bodies. An outstanding question remains if tau pathology can also be seen in patients with Huntington's and Parkinson's disease who had received foetal neural allografts. This was addressed by immunohistochemical/immunofluorescent stainings performed on grafted tissue of two Huntington's disease patients, who came to autopsy 9 and 12 years post-transplantation, and two patients with Parkinson's disease who came to autopsy 18 months and 16 years post-transplantation. We show that grafts also contain tau pathology in both types of transplanted patients. In two patients with Huntington's disease, the grafted tissue showed the presence of hyperphosphorylated tau [both AT8 (phospho-tau Ser202 and Thr205) and CP13 (pSer202) immunohistochemical stainings] pathological inclusions, neurofibrillary tangles and neuropil threads. In patients with Parkinson's disease, the grafted tissue was characterized by hyperphosphorylated tau (AT8; immunofluorescent staining) pathological inclusions, neurofibrillary tangles and neuropil threads but only in the patient who came to autopsy 16 years post-transplantation. Abundant tau-related pathology was observed in the cortex and striatum of all cases studied. While the striatum of the grafted Huntington's disease patient revealed an equal amount of 3-repeat and 4-repeat isoforms of tau, the grafted tissue showed elevated 4-repeat isoforms by western blot. This suggests that transplants may have acquired tau pathology from the host brain, although another possibility is that this was due to acceleration of ageing. This finding not only adds to the recent reports that tau pathology is a feature of these neurodegenerative diseases, but also that tau pathology can manifest in healthy neural tissue transplanted into the brains of patients with two distinct neurodegenerative disorders.