Cyclin' toward dementia: Cell cycle abnormalities and abortive oncogenesis in Alzheimer disease

Recent evidence has associated the aberrant, proximal re-expression of various cell cycle control elements with neuronal vulnerability in Alzheimer disease, a chronic neurodegeneration. Such ectopic localization of various cyclins, cyclin-dependent kinases, and cyclin inhibitors in neurons can be seen as an attempt to re-enter the cell cycle. Given that primary neurons are terminally differentiated, any attempted re-entry into the cell division cycle in this postmitotic environment will be dysregulated. Since successful dysregulation of the cell cycle is also the hallmark of a neoplasm, early cell-cycle pathophysiology in Alzheimer disease may recruit oncogenic signal transduction mechanisms and, hence, can be viewed as an abortive neoplastic transformation. (C) 2000 Wiley-Liss, Inc.