Zhang Jianxin, Fan Wenhui, Su Chen, Jin Zhi
Department of Traditional Chinese Medicine, the Second Hospital of Shandong University, Jinan, 250014, China.
BMC Neurol. 2025 Feb 5;25(1):49. doi: 10.1186/s12883-025-04057-z.
Alzheimer's disease (AD) is one of the most common forms of dementia in the elderly, characterized by progressive neurodegeneration. While the exact etiology of AD remains unclear, immune inflammation is known to play a significant role in the disease.
This study utilized a two-sample Mendelian randomization (MR) approach to assess the causal relationship between different types of immune cells and AD, while considering inflammatory factors as intermediate variables. Data were collected from three sources: immune cell data (731 phenotypes), inflammatory factors (48 cytokines from 8,293 individuals), and AD data (35,274 cases, 59,163 controls). Multiple MR methods were employed to minimize bias, and detailed descriptions of instrumental variable selection and statistical methods were provided.
The study findings suggest potential causal relationships between six different types of immune cells and AD, as well as causal relationships between 13 immune cells and inflammatory factors. Additionally, two statistically significant inflammatory factors were found to have potential causal relationships with AD. Specifically, immune cells CD33-HLA DR + and CD45 on CD33-HLA DR + may further influence AD by regulating Interleukin-2 levels.
This study provides valuable insights into the immunoinflammatory pathogenesis of AD and offers partial guidance for the development of relevant interventions, thereby contributing beneficial information for the prevention and treatment of related diseases.
阿尔茨海默病(AD)是老年人中最常见的痴呆形式之一,其特征为进行性神经退行性变。虽然AD的确切病因尚不清楚,但已知免疫炎症在该病中起重要作用。
本研究采用两样本孟德尔随机化(MR)方法来评估不同类型免疫细胞与AD之间的因果关系,同时将炎症因子视为中间变量。数据收集自三个来源:免疫细胞数据(731种表型)、炎症因子(来自8293人的48种细胞因子)和AD数据(35274例病例,59163例对照)。采用多种MR方法以尽量减少偏差,并提供了工具变量选择和统计方法的详细描述。
研究结果表明六种不同类型的免疫细胞与AD之间存在潜在因果关系,以及13种免疫细胞与炎症因子之间存在因果关系。此外,发现两种具有统计学意义的炎症因子与AD存在潜在因果关系。具体而言,免疫细胞CD33-HLA DR+和CD33-HLA DR+上的CD45可能通过调节白细胞介素-2水平进一步影响AD。
本研究为AD的免疫炎症发病机制提供了有价值的见解,并为相关干预措施的开发提供了部分指导,从而为相关疾病的预防和治疗提供有益信息。