The study by Porayette et al. nicely supports emerging evidence from our lab and others showing that APP metabolites play a role in stem cell biology, including neural stem cells. The study provides insight into the controversial results previously obtained concerning the effect of Aβ on stem cell proliferation, emphasizing the differential effect of a variety of forms and aggregation levels of Aβ on human embryonic stem cell and neural stem cell proliferation and differentiation. Another interesting aspect addressed in this paper is that APP processing, and thus expression of given APP metabolites, is differentially pronounced and modulated during different stages of embryonic development and cell lineage commitment. It would be interesting to further address the role of APP metabolites in the pluripotency-multipotency transition.

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