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|Cycling to Nowhere
The paper by Arendt and colleagues presents compelling evidence for DNA synthesis in terminally differentiated neurons of the AD brain, and raises a number of other questions. It is intriguing to speculate whether the increase in cyclin B1 observed in half of the aged control subjects is indicative of an increased attempt by these aging neurons to re-enter the cell cycle. Is this a precursor stage to MCI? Would these individuals have developed AD if they had lived longer? Does cyclin B1 expression remain elevated after the cells reach tetraploidy?
Given that these polyploidy neurons are unlikely to survive (Yang et al., 2003), it seems likely that the quantitation of polyploidy and cell cycle related markers at the terminal stage of the disease is a gross underestimation of the mitogenic stimulus reaching neurons in the aging brain.
Recently we identified an upregulation in the expression of osteopontin, a protein that is intimately involved in cell cycle progression and cell adhesion (Wung et al., 2007) in the AD brain that may be a...