Dura mater is a potential source of Aβ seeds.
Dura mater is a potential source of Aβ seeds.
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DOI：
10.1007/s00401-016-1565-x
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发表时间：
2016-06
影响因子：
12.7
通讯作者：
Hainfellner JA
中科院分区：
文献类型：
--
作者：
Kovacs GG;Lutz MI;Ricken G;Ströbel T;Höftberger R;Preusser M;Regelsberger G;Hönigschnabl S;Reiner A;Fischer P;Budka H;Hainfellner JA
β淀粉样蛋白（amyloid-β，Aβ）在脑实质和血管中的沉积是阿尔茨海默病（Alzheimer disease，AD）的标志之一。最近在硬脑膜移植或垂体提取物治疗后医源性Creutzfeldt-Jakob病（iCJD）中观察到Aβ沉积，这引起了人们对Aβ是否能够通过疾病相关朊病毒蛋白传播疾病的关注。为了解决这个问题，我们重新采样并重新评估了档案材料，包括两例iCJD患者（28岁和33岁）的移植硬脑膜，他们没有AβPP、PSEN 1和PSEN 2基因突变，并携带APOE基因的ε3/ε3等位基因。此外，我们在基于社区的VITA研究中评价了尸检时获得的84份硬脑膜样本（平均年龄84.9 ± 0.3岁）中是否存在Aβ沉积。我们发现硬脑膜可能以脑淀粉样血管病或无定形聚集物的形式存在Aβ沉积物（13%）。在这两个iCJD病例中，移植的硬脑膜中有Aβ积聚。大脑Aβ沉积的形态和分布模式以及tau病理学的缺乏将iCJD中的Aβ蛋白病与AD区分开来，与携带一个或两个APOE 4等位基因的无认知下降的年轻个体中观察到的Aβ蛋白病区分开来，与创伤性脑损伤相关的Aβ蛋白病区分开来。我们在硬脑膜（包括移植的硬脑膜）中发现了Aβ沉积物，并且在iCJD中发现了不同的脑Aβ分布，这支持了Aβ的播种特性。然而，与朊病毒疾病相反，我们的研究表明，这种Aβ播种不能再现AD的完整临床病理表型。
Deposition of amyloid-β (Aβ) in the brain parenchyma and vessels is one of the hallmarks of Alzheimer disease (AD). Recent observations of Aβ deposition in iatrogenic Creutzfeldt-Jakob disease (iCJD) after dural grafting or treatment with pituitary extracts raised concerns whether Aβ is capable of transmitting disease as seen in prion diseases by the disease-associated prion protein. To address this issue, we re-sampled and re-evaluated archival material, including the grafted dura mater of two cases with iCJD (28 and 33-years-old) without mutations in the AβPP, PSEN1 and PSEN2 genes, and carrying ε3/ε3 alleles of the APOE gene. In addition, we evaluated 84 dura mater samples obtained at autopsy (mean age 84.9 ± 0.3) in the community-based VITA study for the presence of Aβ deposition. We show that the dura mater may harbor Aβ deposits (13 %) in the form of cerebral amyloid angiopathy or amorphous aggregates. In both iCJD cases, the grafted dura mater had accumulated Aβ. The morphology and distribution pattern of cerebral Aβ deposition together with the lack of tau pathology distinguishes the Aβ proteinopathy in iCJD from AD, from that seen in young individuals without cognitive decline carrying one or two APOE4 alleles, and from that related to traumatic brain injury. Our novel findings of Aβ deposits in the dura mater, including the grafted dura, and the distinct cerebral Aβ distribution in iCJD support the seeding properties of Aβ. However, in contrast to prion diseases, our study suggests that such Aβ seeding is unable to reproduce the full clinicopathological phenotype of AD.