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阿爾茲海默癥疾病模型

疾病簡(jiǎn)介

阿爾茲海默癥(Alzheimer's disease,AD),常被稱為老年癡呆?;颊叩呐R床表現(xiàn)為持續(xù)性綜合智力障礙、認(rèn)知功能障礙、精神和行為異常、不能獨(dú)立生活或工作。患者大腦垂死的神經(jīng)元細(xì)胞間會(huì)形成斑塊沉積,神經(jīng)元內(nèi)部出現(xiàn)纏結(jié),海馬體以及其他腦區(qū)呈現(xiàn)廣泛性萎縮。

疾病模型

南模生物長(zhǎng)期致力于神經(jīng)退行性疾病相關(guān)研究,針對(duì)阿爾茲海默癥(AD)自主研發(fā)了一系列大、小鼠模型,可用于發(fā)病機(jī)制探索或藥理藥效研究。

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。

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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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