I am submitting this invited comment with the caveat that I have not had an opportunity to read the full text of this article. With that caveat in mind, it seems to me that this study is the in vivo correlate of the work published by McPhie and colleagues (see ARF related news story
) using forced expression of similar APP sequences in primary neurons. In McPhie's study, cell cycle activation with DNA synthesis preceded apoptotic death of neurons. Assuming the expression of cell cycle proteins in APP23 mice (Gartner et al.) was examined at different time points, including aged mice, I wonder whether primary neurons are a reliable model for studies of cell cycle dysregulation in mature brain. I raised this point during the live cell cycle chat (ARF live discussion
emphasizing the immature nature of primary neuronal cultures—which is exactly the property that allows them to grow in vitro. Yet, McPhie's results are very intriguing—and taken together...