淀粉樣前體蛋白APP與AD有著密切的聯(lián)系,其分解產(chǎn)生的B-淀粉樣蛋AB在腦中的堆積是導(dǎo)致阿爾茨海默病的重要因素。南模生物通過(guò)ES細(xì)胞打靶技術(shù),將小鼠App基因部分替換為人源APPNL-G-F,從而表達(dá)人鼠嵌合APPNL-G-F蛋白,該純合子小鼠隨著年齡增長(zhǎng),大腦會(huì)逐漸出現(xiàn)明顯的斑塊累積癥狀。
Fig1. Detection of APP expression in brain by RT-PCR.
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.
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.
Mutations: APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V
Fig 1. Expression of Aβ in brain of?6-month-old 5xFAD mice.
Fig 2.?ELISA analysis of CSF sample collected from 5xFAD mice for human Aβ42.
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).
Fig 4.?Aβ 6E10 Area? fraction in cortex and hippocampis of?5xFAD mice after Lecanemab treatment.
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