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.

中文翻译：

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亨廷顿氏病和帕金森氏病患者胎儿神经同种异体移植物中tau病理的存在

已经探索了细胞替代作为修复亨廷顿氏病和帕金森氏病患者大脑的治疗策略。在这种情况下，对健康移植组织的验尸评估显示，亨廷顿样或帕金森样病理的发展，包括突变的亨廷顿蛋白聚集体和路易小体。是否还可以在接受胎儿神经同种异体移植的亨廷顿氏病和帕金森氏病患者中观察到tau病理，这仍然是一个悬而未决的问题。这是通过对两名亨廷顿氏病患者的移植组织进行免疫组织化学/免疫荧光染色解决的，这些患者在移植后9和12年进行了尸体解剖，并对两名帕金森氏病患者在移植后18个月和16年进行了尸体解剖。我们表明，在两种类型的移植患者中，移植物还包含tau病理。在两名患有亨廷顿舞蹈病的患者中，移植的组织显示出高磷酸化的tau [AT8（磷酸化tau Ser202和Thr205）和CP13（pSer202）免疫组化染色]病理包涵体，神经原纤维缠结和神经纤维缠结。在帕金森氏病患者中，移植组织的特征是过度磷酸化的tau（AT8;免疫荧光染色）病理包裹体，神经原纤维缠结和神经纤维缠结，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层和纹状体中均观察到大量与tau有关的病理。移植的亨廷顿舞蹈病患者的纹状体显示出tau的3重复和4重复同工型等量，但通过Western印迹显示移植的组织显示4重复同工型升高。这表明移植物可能已经从宿主大脑中获得了tau病理，尽管另一种可能性是这是由于衰老加速所致。这一发现不仅增加了最近的报道，tau病理是这些神经退行性疾病的特征，而且tau病理还可以表现在移植到患有两种不同神经退行性疾病的患者的大脑中的健康神经组织中。尽管另一种可能性是这是由于老化的加速。这一发现不仅增加了最近的报道，tau病理是这些神经退行性疾病的特征，而且tau病理还可以表现在移植到患有两种不同神经退行性疾病的患者的大脑中的健康神经组织中。尽管另一种可能性是这是由于老化的加速。这一发现不仅增加了最近的报道，tau病理是这些神经退行性疾病的特征，而且tau病理还可以表现在移植到患有两种不同神经退行性疾病的患者的大脑中的健康神经组织中。