小柯机器人

德国生物信息处理研究所Gunnar F. Schröder、Dieter Willbold和Lothar Gremer课题组合作在研究中取得进展。他们通过小鼠模型淀粉样蛋白-β（Aβ）纤维的冷冻电镜发现，tg-APPArcSwe纤维与散发性阿尔茨海默病患者体内的纤维相似。相关论文发表在2023年11月16日出版的《自然-神经科学》杂志上。

研究人员利用冷冻电镜解析了来源于六种不同小鼠模型中九种体外Aβ纤维的结构。研究人员在APP/PS1、ARTE10和tg-SwDI模型中发现了新的Aβ纤维结构，而在ARTE10、tg-APPSwe和APP23模型中发现了人类II型纤维折叠。tg-APPArcSwe小鼠具有的Aβ纤维结构与散发性阿尔茨海默病患者体内的人类I型细丝相似。详细评估Aβ纤维结构是选择适当小鼠模型的关键，有助于在临床前研发出新型靶向斑块的治疗药物，和阿尔茨海默病正电子发射断层扫描成像示踪剂。

研究人员表示，具有淀粉样蛋白-β脑病理学的转基因小鼠对于阿尔茨海默病新治疗策略的临床前评估至关重要。然而，目前还没有对这种小鼠体内Aβ与阿尔茨海默病患者大脑中的Aβ进行系统性比较。

附：英文原文

Title: Cryo-EM of Aβ fibrils from mouse models find tg-APPArcSwe fibrils resemble those found in patients with sporadic Alzheimer’s disease

Author: Zielinski, Mara, Peralta Reyes, Fernanda S., Gremer, Lothar, Schemmert, Sarah, Frieg, Benedikt, Schfer, Luisa U., Willuweit, Antje, Donner, Lili, Elvers, Margitta, Nilsson, Lars N. G., Syvnen, Stina, Sehlin, Dag, Ingelsson, Martin, Willbold, Dieter, Schrder, Gunnar F.

Issue&Volume: 2023-11-16

Abstract: The use of transgenic mice displaying amyloid-β (Aβ) brain pathology has been essential for the preclinical assessment of new treatment strategies for Alzheimer’s disease. However, the properties of Aβ in such mice have not been systematically compared to Aβ in the brains of patients with Alzheimer’s disease. Here, we determined the structures of nine ex vivo Aβ fibrils from six different mouse models by cryogenic-electron microscopy. We found novel Aβ fibril structures in the APP/PS1, ARTE10 and tg-SwDI models, whereas the human type II filament fold was found in the ARTE10, tg-APPSwe and APP23 models. The tg-APPArcSwe mice showed an Aβ fibril whose structure resembles the human type I filament found in patients with sporadic Alzheimer’s disease. A detailed assessment of the Aβ fibril structure is key to the selection of adequate mouse models for the preclinical development of novel plaque-targeting therapeutics and positron emission tomography imaging tracers in Alzheimer’s disease.

DOI: 10.1038/s41593-023-01484-4

Source: https://www.nature.com/articles/s41593-023-01484-4

Nature Neuroscience：《自然—神经科学》，创刊于1998年。隶属于施普林格·自然出版集团，最新IF：28.771
官方网址：https://www.nature.com/neuro/
投稿链接：https://mts-nn.nature.com/cgi-bin/main.plex