@inbook{e633296e57434231899347407b171d6f,
title = "Activation of cell cycle proteins in transgenic mice in response to neuronal loss but not a{\ss} and tau pathology",
abstract = "Cell 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 AD hallmarks, amyloid-beta (Aβ) plaques and tau-laden neurofibrillary tangles, remains unclear. We sought to determine whether cell cycle reactivation initiates in direct response to Aβ 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 proteins 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 A{\ss} or tau pathology, but rather appears to be triggered by acute neuronal loss.",
keywords = "Alzheimer's disease, Cdk4, Cell cycle, PCNA, amyloid-beta, apoptosis, phospho-Rb, phospho-histone H3, tetracycline-inducible, transgenic mice",
author = "Lopes, {Joao P.} and Mathew Blurton-Jones and Yamasaki, {Tritia R.} and Paula Agostinho and LaFerla, {Frank M.}",
year = "2011",
doi = "10.3233/978-1-60750-733-8-139",
language = "English",
isbn = "9781607507321",
series = "Advances in Alzheimer's Disease",
pages = "139--148",
editor = "Gemma Casadesus",
booktitle = "Handbook of Animal Models in Alzheimer's Disease",
}