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.

中文翻译：

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FAM222A 编码一种在阿尔茨海默氏病斑块中积累的蛋白质。

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，我们将 FAM222A 报告为假定的脑萎缩易感基因。我们对影像遗传学的交叉表型关联分析表明 FAM222A 与 AD 相关的局部脑萎缩之间存在潜在联系。FAM222A 编码的蛋白质主要在中枢神经系统中表达，并在 AD 患者的大脑和 AD 小鼠模型中增加。它在淀粉样蛋白沉积物中积累，通过其 N 末端 Aβ 结合结构域与淀粉样蛋白-β (Aβ) 发生物理相互作用，并促进 Aβ 聚集。这种蛋白质的脑室内输注或强制表达会加剧 AD 小鼠模型中的神经炎症和认知功能障碍，而这种蛋白质的消融会抑制淀粉样蛋白沉积物的形成，AD 小鼠模型中的神经炎症和认知缺陷。我们的数据支持由 FAM222A 编码的蛋白质在 AD 中的病理相关性。