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Espuny-Camacho I, Arranz AM, Fiers M, Snellinx A, Ando K, Munck S, Bonnefont J, Lambot L, Corthout N, Omodho L, Vanden Eynden E, Radaelli E, Tesseur I, Wray S, Ebneth A, Hardy J, Leroy K, Brion JP, Vanderhaeghen P, De Strooper B. Hallmarks of Alzheimer's Disease in Stem-Cell-Derived Human Neurons Transplanted into Mouse Brain. Neuron. 2017 Mar 8;93(5):1066-1081.e8. Epub 2017 Feb 23 PubMed.
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Ludwig-Maximilians-Universität Munich
It was a pleasure to read this major and excellent paper that documents very elegantly the great potential of human PSCs for the development of better mouse models for AD. I did not expect the technique would be this powerful. This fascinating paper shows, for the first time convincingly in vivo, that human neurons behave differently in response to fibrillary Aß than mouse neurons. It is tempting to speculate that this is due to the expression of 3R/4R tau splice forms in the human neurons, but there could also be other reasons.
It is also difficult to judge if the necrotic nerve cell degeneration of iPSC neurons within the AD mouse brain is a phenomenon that is indeed responsible for nerve cell loss in patients with AD. From a neuropathological point of view, neuronal necrosis to an extent observed in this study is not a typical feature observed in human AD brains, but rather a finding seen in occasions of more acute damage.
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