IRCCS Fondazione Don Carlo Gnocchi, P.zza Morandi, 3, 20100, Milan, Italy.
Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.
Cell Mol Neurobiol. 2019 Nov;39(8):1217-1221. doi: 10.1007/s10571-019-00712-5. Epub 2019 Jul 11.
Alzheimer's disease (AD) is a neurodegenerative disease characterized by a progressive decline in cognitive performance; Mild Cognitive Impairment (MCI) is instead an objective decline in cognitive performance that does not reach pathology. Paired immunoglobulin-like type 2 receptor alpha (PILRA) is a cell surface inhibitory receptor that was recently suggested to be involved in AD pathogenesis. In particular, the arginine-to-glycine substitution in position 78 (R78, rs1859788) was shown to be protective against AD. Herpes simplex virus type 1 (HSV-1) infection is suspected as well to be involved in AD. Interestingly, HSV-1 uses PILRA to infect cells, and HSV-1 infects more efficiently PIRLA G78 compared to R78 macrophages. We analyzed PILRA rs1859788 polymorphism and HSV-1 humoral immune responses in AD (n = 61) and MCI patients (n = 48), and in sex and age matched healthy controls (HC; n = 57). The rs1859788 PILRA genotype distribution was similar among AD, MCI and HC; HSV-1 antibody (Ab) titers were increased in AD and MCI compared to HC (p < 0.05 for both comparisons). Notably, HSV-1-specific IgG1 were significantly increased in AD patients carrying PILRA R78 rs1859788 AA than in those carrying G78 AG or GG (p = 0.01 for both comparisons), and the lowest titers of HSV-1-specific IgG1 were observed in rs1859788 GG AD. HSV-1 IgG are increased in AD patients with the protective R78 PILRA genotype. Because in AD patients brain atrophy is inversely correlated with HSV-1-specific IgG titers, results herein suggest a possible link between two important genetic and infective factors suspected to be involved in AD pathogenesis.
阿尔茨海默病（AD）是一种神经退行性疾病，其特征是认知表现逐渐下降；轻度认知障碍（MCI）则是认知表现的客观下降，但未达到病理学程度。配对免疫球蛋白样 2 型受体 alpha（PILRA）是一种细胞表面抑制受体，最近被认为与 AD 的发病机制有关。特别是位置 78 的精氨酸到甘氨酸取代（R78，rs1859788）被证明对 AD 具有保护作用。单纯疱疹病毒 1 型（HSV-1）感染也被怀疑与 AD 有关。有趣的是，HSV-1 使用 PILRA 感染细胞，并且 HSV-1 比 R78 巨噬细胞更有效地感染 PILRA G78。我们分析了 AD（n=61）和 MCI 患者（n=48）以及性别和年龄匹配的健康对照者（HC；n=57）中 PILRA rs1859788 多态性和 HSV-1 体液免疫反应。AD、MCI 和 HC 之间的 rs1859788 PILRA 基因型分布相似；与 HC 相比，AD 和 MCI 中的 HSV-1 抗体（Ab）滴度增加（两种比较均 p<0.05）。值得注意的是，与携带 G78 AG 或 GG 的 PILRA R78 rs1859788 AA 的 AD 患者相比，携带 PILRA R78 rs1859788 AA 的 AD 患者的 HSV-1 特异性 IgG1 显著增加（两种比较均 p=0.01），并且在 rs1859788 GG AD 中观察到 HSV-1 特异性 IgG1 的最低滴度。在具有保护性 R78 PILRA 基因型的 AD 患者中，HSV-1 IgG 增加。由于在 AD 患者中，脑萎缩与 HSV-1 特异性 IgG 滴度呈负相关，因此本研究结果提示，在两个可能与 AD 发病机制有关的重要遗传和感染因素之间可能存在关联。
