Amyloid

Aggregates of Amyloid beta induce neuronal cell cycle

Neurons subject to degeneration in Alzheimer's disease (AD) exhibit evidence of re-entry into a mitotic cell cycle even before the development of substantial AD brain pathology. In efforts to identify the initiating factors underlying these cell cycle events , authors have characterized the appearance of the neuronal cell cycle events in the genomic-based transgenic mouse model of AD. Notably, the genomic-based transgenic mice exhibit neuronal cell cycle events in a reproducible temporal and spatial pattern that recapitulates the neuronal vulnerability seen in human AD. Neuronal cell cycle events first appear at 6 months in the frontal cortex layers II/III. This is 6-8 months before detectable amyloid beta (Abeta) deposition, suggesting that specific amyloid precursor protein (APP) processing products are responsible for the induction of neuronal cell cycle events. Furthermore, a reduction in the levels of Abeta dramatically delays the appearance of neuronal cell cycle events. More significantly, elimination of beta-secretase activity blocks the appearance of cell cycle events, providing direct genetic evidence that the amyloidogenic processing of APP is required for the induction of cell cycle events. Finally, in vitro preparations of oligomeric, but not monomeric, Abeta induce DNA synthesis in dissociated cortical neurons, and this response is blocked by antioligomer specific antibodies. Together, our data suggest that low molecular weight aggregates of Abeta induce neuronal cell cycle re-entry in mouse models of Alzheimer's disease. http://www.medicalnewstoday.com