King's College London, Institute of Psychiatry, De Crespigny Park, London, UK.
Neurobiol Aging. 2012 Aug;33(8):1843.e9-17. doi: 10.1016/j.neurobiolaging.2011.12.036. Epub 2012 Feb 1.
Alzheimer's disease (AD) and age-related macular degeneration (AMD) are both neurodegenerative disorders which share common pathological and biochemical features of the complement pathway. The aim of this study was to investigate whether there is an association between well replicated AMD genetic risk factors and AD. A large cohort of AD (n = 3898) patients and controls were genotyped for single nucleotide polymorphisms (SNPs) in the complement factor H (CFH), the Age-related maculopathy susceptibility protein 2 (ARMS2) the complement component 2 (C2), the complement factor B (CFB), and the complement component 3 (C3) genes. While significant but modest associations were identified between the complement factor H, the age-related maculopathy susceptibility protein 2, and the complement component 3 single nucleotide polymorphisms and AD, these were different in direction or genetic model to that observed in AMD. In addition the multilocus genetic model that predicts around a half of the sibling risk for AMD does not predict risk for AD. Our study provides further support to the hypothesis that while activation of the alternative complement pathway is central to AMD pathogenesis, it is less involved in AD.
阿尔茨海默病（AD）和年龄相关性黄斑变性（AMD）都是神经退行性疾病，它们具有补体途径的共同病理和生化特征。本研究旨在探讨经过充分复制的 AMD 遗传风险因素与 AD 是否存在关联。对一大群 AD（n=3898）患者和对照进行了补体因子 H（CFH）、年龄相关性黄斑变性易感性蛋白 2（ARMS2）、补体成分 2（C2）、补体因子 B（CFB）和补体成分 3（C3）基因的单核苷酸多态性（SNP）基因分型。虽然在补体因子 H、年龄相关性黄斑变性易感性蛋白 2 和补体成分 3 的单核苷酸多态性与 AD 之间存在显著但适度的关联，但这些关联在方向或遗传模型上与 AMD 观察到的不同。此外，预测 AMD 约一半同胞风险的多基因遗传模型并不能预测 AD 的风险。我们的研究进一步支持了这样一种假设，即尽管补体替代途径的激活是 AMD 发病机制的核心，但它在 AD 中的参与程度较低。
