The molecular fidelity of Aβ pathology in 5xFAD and AppNL-FPsen1P117L mice revealed by cryo-EM

	The molecular fidelity of Aβ pathology in 5xFAD and AppNL-FPsen1P117L mice revealed by cryo-EM
	Song, MA; Zheng, HR; Han, JT; Xu, KY; Zhang, DF; Cao, Q
	2026
发表期刊	Mol. Neurodegener.
卷号	21 期号:1
摘要	Animal models, particularly mouse models, are indispensable for understanding the pathogenic mechanisms and developing therapeutic and diagnostic drugs for Alzheimer's diseases (AD). While most AD mouse models aim to mimic amyloid-beta (A beta) pathology in their brains, previous research has demonstrated that not all models succeed in reproducing A beta fibril structures observed in the brains of AD patients. In this study, we determined cryo-electron microscopy (cryo-EM) structures of A beta fibrils extracted from the brains of two AD models, 5xFAD and App(NL-F)Psen1(P117L). The former represents one of the most widely used transgenic AD models, while the latter is the third-generation knock-in model designed to address the issues arising from App overexpression in conventional models. Our results revealed that fibrils from the 5xFAD mouse exhibit a structure nearly identical to human Type II A beta fibrils found in AD patients, whereas the App(NL-F)Psen1(P117L) mouse predominantly possesses Type II A beta fibrils but also contains another A beta fibril species. A subtle discrepancy in main chain arrangement at the position of Val36 was noted among all reported human and mouse Type II structures, potentially originating from variations in the brain microenvironment between human and mice. In conclusion, our findings validated the replication of A beta pathology in 5xFAD and App(NL-F)Psen1(P117L) mice and provide additional options for selecting appropriate animal models in studies necessitating molecular-level replication of A beta structures
收录类别	SCIE
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/14981
专题	科研部门_复杂疾病表观遗传机制与模型(张登峰）
推荐引用方式 GB/T 7714	Song, MA,Zheng, HR,Han, JT,et al. The molecular fidelity of Aβ pathology in 5xFAD and AppNL-FPsen1P117L mice revealed by cryo-EM[J]. Mol. Neurodegener.,2026,21(1).
APA	Song, MA,Zheng, HR,Han, JT,Xu, KY,Zhang, DF,&Cao, Q.(2026).The molecular fidelity of Aβ pathology in 5xFAD and AppNL-FPsen1P117L mice revealed by cryo-EM.Mol. Neurodegener.,21(1).
MLA	Song, MA,et al."The molecular fidelity of Aβ pathology in 5xFAD and AppNL-FPsen1P117L mice revealed by cryo-EM".Mol. Neurodegener. 21.1(2026).

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