Vascular variant of prion protein cerebral amyloidosis with tau-positive neurofibrillary tangles: The phenotype of the stop codon 145 mutation in PRNP
Vascular variant of prion protein cerebral amyloidosis with tau-positive neurofibrillary tangles: The phenotype of the stop codon 145 mutation in PRNP
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DOI：
10.1073/pnas.93.2.744
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发表时间：
1996-01-23
影响因子：
11.1
通讯作者：
Tagliavini, F
中科院分区：
文献类型：
--
作者：
Ghetti, B;Piccardo, P;Tagliavini, F
PrP 淀粉样蛋白在脑血管中的沉积以及神经原纤维病变是痴呆的神经病理学标志，与 PRNP 密码子 145 处的终止突变相关，PRNP 是编码朊病毒蛋白 (PrP) 的基因。在这种疾病中，组织切片中的血管淀粉样蛋白和从淀粉样蛋白中提取的大约 7.5 kDa 片段被位于 PrP 序列（包括氨基酸 90-147）中的表位抗体标记，富含淀粉样蛋白的血管也被 C 末端抗体标记，表明来自正常等位基因的 PrP 参与了病理过程。大脑灰质中存在丰富的神经原纤维病变，它们由成对的螺旋丝组成，标记有识别tau蛋白多个磷酸化位点的抗体，与阿尔茨海默病中观察到的类似，在PRNP突变引起的疾病或人类传染性海绵状脑病中尚未报道过PrP脑淀粉样血管病；我们建议将这种表型命名为 PrP 脑淀粉样血管病 (PrP-CAA)。
Deposition of PrP amyloid in cerebral vessels in conjunction with neurofibrillary lesions is the neuropathologic hallmark of the dementia associated with a stop mutation at codon 145 of PRNP, the gene encoding the prion protein (PrP), In this disorder, the vascular amyloid in tissue sections and the approximate to 7.5-kDa fragment extracted from amyloid are labeled by antibodies to epitopes located in the PrP sequence including amino acids 90-147, Amyloid laden vessels are also labeled by antibodies against the C terminus, suggesting that PrP from the normal allele is involved in the pathologic process. Abundant neurofibrillary lesions are present in the cerebral gray matter, They are composed of paired helical filaments, are labeled with antibodies that recognize multiple phosphorylation sites in tau protein, and are similar to those observed in Alzheimer disease, A PrP cerebral amyloid angiopathy has not been reported in diseases caused by PRNP mutations or in human transmissible spongiform encephalopathies; we propose to name this phenotype PrP cerebral amyloid angiopathy (PrP-CAA).