Activation of cell cycle proteins in transgenic mice in response to neuronal loss but not aß and tau pathology

Joao P. Lopes, Mathew Blurton-Jones, Tritia R. Yamasaki, Paula Agostinho, Frank M. LaFerla

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review


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 Aß or tau pathology, but rather appears to be triggered by acute neuronal loss.

Original languageEnglish
Title of host publicationHandbook of Animal Models in Alzheimer's Disease
EditorsGemma Casadesus
Number of pages10
StatePublished - 2011

Publication series

NameAdvances in Alzheimer's Disease
ISSN (Print)2210-5727
ISSN (Electronic)2210-5735


  • Alzheimer's disease
  • Cdk4
  • Cell cycle
  • PCNA
  • amyloid-beta
  • apoptosis
  • phospho-Rb
  • phospho-histone H3
  • tetracycline-inducible
  • transgenic mice

ASJC Scopus subject areas

  • Clinical Neurology


Dive into the research topics of 'Activation of cell cycle proteins in transgenic mice in response to neuronal loss but not aß and tau pathology'. Together they form a unique fingerprint.

Cite this