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Evidence for human transmission of amyloid-beta pathology and cerebral amyloid angiopathy

机译：人类传播淀粉样β病理和脑淀粉样血管病的证据

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摘要

More than two hundred individuals developed Creutzfeldt-Jakob disease (CJD) worldwide as a result of treatment, typically in childhood, with human cadaveric pituitary-derived growth hormone contaminated with prions(1,2). Although such treatment ceased in 1985, iatrogenic CJD (iCJD) continues to emerge because of the prolonged incubation periods seen in human prion infections. Unexpectedly, in an autopsy study of eight individuals with iCJD, aged 36-51 years, in four we found moderate to severe grey matter and vascular amyloid-beta (A beta) pathology. The A beta deposition in the grey matter was typical of that seen in Alzheimer's disease and A beta in the blood vessel walls was characteristic of cerebral amyloid angiopathy(3) and did not co-localize with prion protein deposition. None of these patients had pathogenic mutations, APOE epsilon 4 or other high-risk alleles(4) associated with early-onset Alzheimer's disease. Examination of a series of 116 patients with other prion diseases from a prospective observational cohort study(5) showed minimal or no A beta pathology in cases of similar age range, or a decade older, without APOE epsilon 4 risk alleles. We also analysed pituitary glands from individuals with A beta pathology and found marked A beta deposition in multiple cases. Experimental seeding of A beta pathology has been previously demonstrated in primates and transgenic mice by central nervous system or peripheral inoculation with Alzheimer's disease brain homogenate(6-11). The marked deposition of parenchymal and vascular A beta in these relatively young patients with iCJD, in contrast with other prion disease patients and population controls, is consistent with iatrogenic transmission of A beta pathology in addition to CJD and suggests that healthy exposed individuals may also be at risk of iatrogenic Alzheimer's disease and cerebral amyloid angiopathy. These findings should also prompt investigation of whether other known iatrogenic routes of prion transmission may also be relevant to A beta and other proteopathic seeds associated with neurodegenerative and other human diseases.
机译：在全世界范围内，有200多个个体因治疗（通常在儿童时期）被人体体垂体衍生的生长激素污染了病毒而发展为Creutzfeldt-Jakob病（CJD）（1,2）。尽管这种治疗在1985年停止，但由于在人类病毒感染中潜伏期延长，医源性CJD（iCJD）继续出现。出乎意料的是，在对8名36-51岁的iCJD患者进行的尸检研究中，有4名患者发现中度至重度灰质和血管淀粉样β（A beta）病理。灰质中的Aβ沉积是阿尔茨海默氏病的典型特征，血管壁中的Aβ是脑淀粉样血管病的特征（3），并且与病毒蛋白沉积不共存。这些患者均无致病性突变，APOE epsilon 4或与早发性阿尔茨海默氏病相关的其他高风险等位基因（4）。在一项前瞻性观察性队列研究中对一系列116例其他病毒疾病患者进行了检查（5），结果显示在年龄相似或十岁以上且无APOEε4风险等位基因的病例中，Aβ病变极小或无。我们还分析了患有Aβ病理学的个体的垂体腺，并在多个病例中发现了明显的Aβ沉积。先前已在灵长类动物和转基因小鼠中通过中枢神经系统或外周接种阿尔茨海默氏病脑匀浆（6-11）证明了Aβ病理学的实验播种。与其他病毒病患者和人群对照相比，在这些相对年轻的iCJD患者中，实质和血管A beta的明显沉积与CJD之外的医源性A beta病理学相一致，这表明健康暴露的个体也可能是有医源性阿尔茨海默氏病和脑淀粉样血管病的风险。这些发现也应促使人们调查investigation病毒传播的其他已知医源性途径是否也可能与Aβ和其他与神经退行性疾病和其他人类疾病有关的蛋白性种子有关。

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  • 来源
    《Nature》 |2015年第7568期|247-250|共4页
  • 作者

    Jaunmuktane Zane; Mead Simon; Ellis Matthew; Wadsworth Jonathan D. F.; Nicoll Andrew J.; Kenny Joanna; Launchbury Francesca; Linehan Jacqueline; Richard-Loendt Angela; Walker A. Sarah; Rudge Peter; Collinge John; Brandner Sebastian;

  • 作者单位

    Natl Hosp Neurol & Neurosurg, Div Neuropathol, London WC1N 3BG, England;

    MRC, Prion Unit, London WC1 3BG, England|UCL Inst Neurol, Dept Neurodegenerat Dis, London WC1N 3BG, England|Natl Hosp Neurol & Neurosurg, Natl Prion Clin, London WC1N 3BG, England;

    UCL Inst Neurol, Dept Neurodegenerat Dis, London WC1N 3BG, England;

    MRC, Prion Unit, London WC1 3BG, England|UCL Inst Neurol, Dept Neurodegenerat Dis, London WC1N 3BG, England;

    MRC, Prion Unit, London WC1 3BG, England|UCL Inst Neurol, Dept Neurodegenerat Dis, London WC1N 3BG, England;

    MRC, Prion Unit, London WC1 3BG, England|Natl Hosp Neurol & Neurosurg, Natl Prion Clin, London WC1N 3BG, England;

    UCL Inst Neurol, Dept Neurodegenerat Dis, London WC1N 3BG, England;

    MRC, Prion Unit, London WC1 3BG, England;

    UCL Inst Neurol, Dept Neurodegenerat Dis, London WC1N 3BG, England;

    UCL, MRC Clin Trials Unit, London WC2B 6NH, England;

    MRC, Prion Unit, London WC1 3BG, England|Natl Hosp Neurol & Neurosurg, Natl Prion Clin, London WC1N 3BG, England;

    MRC, Prion Unit, London WC1 3BG, England|UCL Inst Neurol, Dept Neurodegenerat Dis, London WC1N 3BG, England|Natl Hosp Neurol & Neurosurg, Natl Prion Clin, London WC1N 3BG, England;

    Natl Hosp Neurol & Neurosurg, Div Neuropathol, London WC1N 3BG, England|MRC, Prion Unit, London WC1 3BG, England|UCL Inst Neurol, Dept Neurodegenerat Dis, London WC1N 3BG, England;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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