The antagonistic pleiotropy (AP) theory posits that adaptive evolutionary changes, which facilitate reproduction and individual fitness early in life, can enhance detrimental aging-related processes. Several genes associated with human brain diseases play a protective role in infection, suggesting the relevance of AP in the context of brain aging and neurodegeneration. Relatedly, genetic variants that confer immune protection against pathogens may lead to uncontrolled brain inflammation later in life. Here, we propose a conceptual framework suggesting that the pleiotropic roles of genes in infections and host–pathogen interactions should be considered when studying neurological illnesses. We reinterpret recent findings regarding the impact of neurological disease-associated genetic traits on infections and chronic inflammatory diseases. Identifying the AP pathways shared among these seemingly unrelated conditions might provide further insights into the detrimental role of the immune system in brain disease as well as the mechanisms involved in chronic infections.

拮抗多效性 (AP) 理论认为，促进生命早期繁殖和个体健康的适应性进化变化可以增强有害的衰老相关过程。几个与人类大脑疾病相关的基因在感染中发挥保护作用，表明 AP 与大脑衰老和神经退行性疾病的相关性。相关地，赋予针对病原体的免疫保护的遗传变异可能导致生命后期不受控制的脑部炎症。在这里，我们提出了一个概念框架，表明在研究神经系统疾病时应该考虑基因在感染和宿主 - 病原体相互作用中的多效作用。我们重新解释了最近关于神经系统疾病相关遗传特征对感染和慢性炎症疾病的影响的发现。