Activation of cell cycle proteins in transgenic mice in response to neuronal loss but not amyloid-beta and tau pathology.

TitleActivation of cell cycle proteins in transgenic mice in response to neuronal loss but not amyloid-beta and tau pathology.
Publication TypeJournal Article
Year of Publication2009
JournalJournal of Alzheimer's disease : JAD
Volume16
Issue3
Pagination541-9
Date Published2009
ISSN1387-2877
AbstractCell cycle proteins are elevated in the brain of patients and in transgenic models of Alzheimer's disease (AD), suggesting that aberrant cell cycle re-entry plays a key role in this disorder. However, the precise relationship between cell cycle reactivation and the hallmarks of AD, amyloid-beta (Abeta) plaques and tau-laden neurofibrillary tangles, remains unclear. We sought to determine whether cell cycle reactivation initiates in direct response to Abeta and tau accumulation or whether it occurs as a downstream consequence of neuronal death pathways. Therefore, we used a triple transgenic mouse model of AD (3xTg-AD) that develops plaques and tangles, but does not exhibit extensive neuronal loss, whereas to model hippocampal neuronal death a tetracycline-regulatable transgenic model of neuronal ablation (CaM/Tet-DT(A) mice) was used. Cell-cycle protein activation was determined in these two models of neurodegeneration, using biochemical and histological approaches. Our findings indicate that Cdk4, PCNA and phospho-Rb are significantly elevated in CaM/Tet-DT(A) mice following neuronal death. In contrast, no significant activation of cell-cycle proteins occurs in 3xTg-AD mice versus non-transgenic controls. Taken together, our data indicate that neuronal cell cycle reactivation is not a prominent feature induced by Abeta or tau pathology, but rather appears to be triggered by acute neuronal loss.
URLhttps://content.iospress.com/openurl?genre=article&issn=1387-2877&volume=16&issue=3&spage=541
DOI10.3233/JAD-2009-0993
PubMed Linkhttp://www.ncbi.nlm.nih.gov/pubmed/19276549?dopt=Abstract
Short TitleJ Alzheimers Dis