Department of Pathology and Molecular Medicine, Third Faculty of Medicine, Charles University and Thomayer University Hospital, Videnska 800, 4-Krc, 14059 Prague, Czech Republic.
Department of Pathology, First Faculty of Medicine, Charles University, and General University Hospital, 4-Krc, 14059 Prague, Czech Republic.
Int J Mol Sci. 2021 Feb 20;22(4):2099. doi: 10.3390/ijms22042099.
Alzheimer's disease (AD) and sporadic Creutzfeldt-Jakob disease (sCJD) are both characterized by extracellular pathologically conformed aggregates of amyloid proteins-amyloid β-protein (Aβ) and prion protein (PrP), respectively. To investigate the potential morphological colocalization of Aβ and PrP aggregates, we examined the hippocampal regions (archicortex and neocortex) of 20 subjects with confirmed comorbid AD and sCJD using neurohistopathological analyses, immunohistochemical methods, and confocal fluorescent microscopy. Our data showed that extracellular Aβ and PrP aggregates tended to be, in most cases, located separately, and "compound" plaques were relatively rare. We observed PrP plaque-like structures in the periphery of the non-compact parts of Aβ plaques, as well as in tau protein-positive dystrophic structures. The AD ABC score according to the NIA-Alzheimer's association guidelines, and prion protein subtype with codon 129 methionine-valine (M/V) polymorphisms in sCJD, while representing key characteristics of these diseases, did not correlate with the morphology of the Aβ/PrP co-aggregates. However, our data showed that PrP aggregation could dominate during co-aggregation with non-compact Aβ in the periphery of Aβ plaques.
阿尔茨海默病（AD）和散发性克雅氏病（sCJD）的特征均为细胞外淀粉样蛋白病理构象聚集，分别为淀粉样 β 蛋白（Aβ）和朊病毒蛋白（PrP）。为了研究 Aβ和 PrP 聚集物的潜在形态共定位，我们使用神经组织病理学分析、免疫组织化学方法和共聚焦荧光显微镜检查了 20 例 AD 和 sCJD 合并症患者的海马区（古皮质和新皮质）。我们的数据表明，细胞外 Aβ和 PrP 聚集物通常分别定位，“复合”斑块相对较少。我们观察到 PrP 斑块样结构位于 Aβ 斑块非致密部分的周边，以及在 tau 蛋白阳性的神经原纤维缠结结构中。根据 NIA-阿尔茨海默病协会指南的 AD ABC 评分，以及 sCJD 中 129 密码子蛋氨酸-缬氨酸（M/V）多态性的朊病毒蛋白亚型，虽然代表了这些疾病的关键特征，但与 Aβ/PrP 共聚集物的形态无关。然而，我们的数据表明，在 Aβ 斑块周边非致密 Aβ 与 PrP 聚集物共聚集时，PrP 聚集可能占主导地位。
