阿尔兹海默症疾病模型

疾病简介

阿尔兹海默症(Alzheimer's disease,AD),常被称为老年痴呆。患者的临床表现为持续性综合智力障碍、认知功能障碍、精神和行为异常、不能独立生活或工作。患者大脑垂死的神经元细胞间会形成斑块沉积,神经元内部出现缠结,海马体以及其他脑区呈现广泛性萎缩。

疾病模型

南模生物长期致力于神经退行性疾病相关研究,针对阿尔兹海默症(AD)自主研发了一系列大、小鼠模型,可用于发病机制探索或药理药效研究。

淀粉样前体蛋白APP与AD有着密切的联系,其分解产生的B-淀粉样蛋AB在脑中的堆积是导致阿尔茨海默病的重要因素。南模生物通过ES细胞打靶技术,将小鼠App基因部分替换为人源APPNL-G-F,从而表达人鼠嵌合APPNL-G-F蛋白,该纯合子小鼠随着年龄增长,大脑会逐渐出现明显的斑块累积症状。

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Fig1. Detection of APP expression in brain by RT-PCR.


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Fig2. (A) β-Amyloid (6E10) staining of WT and hAPPNL-G-F mice at 1, 3 and 6 months (magnification, 40x and 100x). (B) Statistics of 6E10 positive plaque area.


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Fig3. (A) Thioflavine S staining of WT and hAPPNL-G-F mice at 1, 3 and 6 months (magnification, 40x and 100x). (B) Statistics of ThiS positive plaque area.


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Mutations: APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V

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Fig 1. Expression of Aβ in brain of 6-month-old 5xFAD mice.

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Fig 2. ELISA analysis of CSF sample collected from 5xFAD mice for human Aβ42.

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Fig 3. Results of Aβ 6E10 and Iba1 immunocostaining in 5xFAD mice after 3 months of Lecanemab treatment (90mpk, Q2W; n=6, male; dosing started at 7w).

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Fig 4. Aβ 6E10 Area  fraction in cortex and hippocampis of 5xFAD mice after Lecanemab treatment.


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