Re-entry into the cell cycle: a mechanism for neurodegeneration in Alzheimer disease

Several recent findings demonstrated increased expression of cell cycle-rel ated proteins in the degenerating neurons found in Alzheimer disease. We hy pothesize that this apparent attempt to re-enter the cell cycle is a neuron al response to external growth stimuli that leads to an abortive re-entry i nto the cell cycle. However, since neurons of adults apparently lack the ca pacity both to divide in vivo and in vitro, it is possible that they lack t he components necessary to complete the cell division process. Nonetheless, the importance of these findings is that they provide an explanation for t he increased phosphorylation of cytoskeletal proteins such as tau and neuro filaments that represent the most striking intracellular changes in the dis ease. Further, it is our contention that inappropriate re-entry into the ce ll cycle and interrupted mitotic processes are significant factors not only in the cytoskeletal pathology but also in the neuronal degeneration that c haracterizes the pathology of Alzheimer disease.