Activation of p53 in Down Syndrome and in the Ts65Dn Mouse Brain is Associated with a Pro-Apoptotic Phenotype

Antonella Tramutola, Gilda Pupo, Fabio Di Domenico, Eugenio Barone, Andrea Arena, Chiara Lanzillotta, Diede Broekaart, Carla Blarzino, Elizabeth Head, D. Allan Butterfield, Marzia Perluigi

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


Down syndrome (DS) is the most common genetic cause of intellectual disability, resulting from trisomy of chromosome 21. The main feature of DS neuropathology includes early onset of Alzheimer's disease (AD), with deposition of senile plaques and tangles. We hypothesized that apoptosis may be activated in the presence of AD neuropathology in DS, thus we measured proteins associated with upstream and downstream pathways of p53 in the frontal cortex from DS cases with and without AD pathology and from Ts65Dn mice, at different ages. We observed increased acetylation and phosphorylation of p53, coupled to reduced MDM2/p53 complex level and lower levels of SIRT1. Activation of p53 was associated with a number of targets (BAX, PARP1, caspase-3, p21, heat shock proteins, and PGC1α) that were modulated in both DS and DS/AD compared with age-matched controls. In particular, the most relevant changes (increased p-p53 and acetyl-p53 and reduced formation of MDM2/p53 complex) were found to be modified only in the presence of AD pathology in DS. In addition, a similar pattern of alterations in the p53 pathway was found in Ts65Dn mice. These results suggest that p53 may integrate different signals, which can result in a pro-apoptotic-phenotype contributing to AD neuropathology in people with DS.

Original languageEnglish
Pages (from-to)359-371
Number of pages13
JournalJournal of Alzheimer's Disease
Issue number1
StatePublished - Apr 26 2016

Bibliographical note

Publisher Copyright:
© 2016 IOS Press and the authors. All rights reserved.


  • Apoptosis
  • Ts65Dn mouse model
  • caspase
  • p53
  • sirtuins
  • trisomy 21

ASJC Scopus subject areas

  • General Neuroscience
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health


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