Department of Pathology, Case Western Reserve University, Cleveland, OH, USA.
Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA.
Nat Commun. 2020 Jan 21;11(1):411. doi: 10.1038/s41467-019-13962-0.
Alzheimer's disease (AD) is characterized by amyloid plaques and progressive cerebral atrophy. Here, we report FAM222A as a putative brain atrophy susceptibility gene. Our cross-phenotype association analysis of imaging genetics indicates a potential link between FAM222A and AD-related regional brain atrophy. The protein encoded by FAM222A is predominantly expressed in the CNS and is increased in brains of patients with AD and in an AD mouse model. It accumulates within amyloid deposits, physically interacts with amyloid-β (Aβ) via its N-terminal Aβ binding domain, and facilitates Aβ aggregation. Intracerebroventricular infusion or forced expression of this protein exacerbates neuroinflammation and cognitive dysfunction in an AD mouse model whereas ablation of this protein suppresses the formation of amyloid deposits, neuroinflammation and cognitive deficits in the AD mouse model. Our data support the pathological relevance of protein encoded by FAM222A in AD.
阿尔茨海默病（AD）的特征是淀粉样斑块和进行性脑萎缩。在这里，我们报告 FAM222A 是一个潜在的脑萎缩易感性基因。我们对影像学遗传学的跨表型关联分析表明，FAM222A 与 AD 相关的区域性脑萎缩之间存在潜在联系。FAM222A 编码的蛋白主要在中枢神经系统中表达，在 AD 患者的大脑中和 AD 小鼠模型中增加。它在淀粉样沉积物内积累，通过其 N 端 Aβ 结合域与 Aβ 物理相互作用，并促进 Aβ 聚集。该蛋白的脑室内输注或强制表达会加重 AD 小鼠模型中的神经炎症和认知功能障碍，而该蛋白的缺失会抑制 AD 小鼠模型中淀粉样沉积物、神经炎症和认知缺陷的形成。我们的数据支持 FAM222A 编码的蛋白在 AD 中的病理相关性。
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