Infante Jon, Llorca Javier, Rodero Lucía, Palacio Enrique, Berciano José, Combarros Onofre
Service of Neurology, University Hospital Marqués de Valdecilla, University of Cantabria, 39008 Santander, Spain.
Neurosci Lett. 2002 Nov 8;332(3):213-5. doi: 10.1016/s0304-3940(02)00941-2.
Alzheimer's disease (AD) and prion diseases are associated with the occurrence of protein aggregates called amyloid fibrils, containing the amyloid-beta peptide in AD, and a modified form (PrP(Sc)) of the normal cellular prion protein (PrP(c)) in prion diseases. PrP(c) is encoded by the prion protein gene, and a common polymorphism at codon 129 of this gene is a determinant of susceptibility to acquired and sporadic prion diseases but not for sporadic AD. A recently identified novel protein, named Doppel, shares biochemical and structural homology with PrP(c). Preliminary evidence in a German population indicates that a polymorphism at codon 174 of the prion-like protein (PRND) gene encoding for Doppel protein is a predisposing factor for both prion diseases and sporadic AD. A case-control study utilizing a clinically well-defined group of 283 sporadic AD patients and 288 control subjects was performed to test this association. The current study does not demonstrate any significant difference in T174M PRND genotype or allele frequencies between AD patients and controls. Our study in the Spanish population argues against the hypothesis that the PRND gene is causally related to AD.
阿尔茨海默病（AD）和朊病毒疾病与称为淀粉样原纤维的蛋白质聚集体的出现有关，AD中含有β淀粉样肽，而朊病毒疾病中含有正常细胞朊病毒蛋白（PrP(c)）的一种修饰形式（PrP(Sc)）。PrP(c)由朊病毒蛋白基因编码，该基因第129密码子处的常见多态性是获得性和散发性朊病毒疾病易感性的决定因素，但不是散发性AD的决定因素。最近鉴定出一种名为多配体蛋白聚糖（Doppel）的新型蛋白质，它与PrP(c)具有生化和结构同源性。德国人群的初步证据表明，编码多配体蛋白聚糖蛋白的类朊病毒蛋白（PRND）基因第174密码子处的多态性是朊病毒疾病和散发性AD的一个易感因素。利用一组临床明确的283例散发性AD患者和288例对照受试者进行了一项病例对照研究，以检验这种关联。目前的研究未显示AD患者和对照之间T174M PRND基因型或等位基因频率有任何显著差异。我们在西班牙人群中的研究反对PRND基因与AD存在因果关系这一假说。
