Markx Daniel, Loos Cornelia, Claus Stephanie, Haupt Christian, Mawrin Christian, Fändrich Marcus
Institute of Protein Biochemistry, Ulm University, Helmholtzstr. 8/1, 89081 Ulm, Germany.
Institute of Neuropathology, Otto-von-Guericke University, Leipziger Str. 44, 39120 Magdeburg, Germany.
Biochem Biophys Res Commun. 2018 Mar 11;497(3):857-862. doi: 10.1016/j.bbrc.2018.02.137. Epub 2018 Feb 16.
Intracerebral injection of brain extracts from Alzheimer's disease (AD) patients into appropriate mouse models was previously found to drastically accelerate the deposition of Aβ amyloid in the recipient animals indicating a prion-like activity. In this study we show that this prion-like activity can be also identified by using a cell culture model of Aβ plaque formation. Analysis of biochemical fractions of AD brain extract indicate that the seeding-activity correlated with the presence of Aβ peptide and Aβ-derived aggregates. In vitro-formed fibrils were also active but their activity was low and depending on the fibril structure and conditions of fibril formation. Our data indicate a conformational basis of the observed seeding effect and suggest the utility of our cell model for further studies on the prion-like activity of AD extracts.
先前发现,将阿尔茨海默病(AD)患者的脑提取物脑内注射到合适的小鼠模型中,可显著加速受体动物中Aβ淀粉样蛋白的沉积,这表明其具有类朊病毒活性。在本研究中,我们表明这种类朊病毒活性也可以通过使用Aβ斑块形成的细胞培养模型来鉴定。对AD脑提取物的生化组分分析表明,种子活性与Aβ肽和Aβ衍生聚集体的存在相关。体外形成的原纤维也具有活性,但其活性较低,且取决于原纤维结构和原纤维形成条件。我们的数据表明了所观察到的种子效应的构象基础,并提示我们的细胞模型可用于进一步研究AD提取物的类朊病毒活性。