An investigation of the molecular mechanisms engaged before and after the development of Alzheimer disease neuropathology in Down syndrome: A proteomics approach

Giovanna Cenini, Ada Fiorini, Rukhsana Sultana, Marzia Perluigi, Jian Cai, Jon B. Klein, Elizabeth Head, D. Allan Butterfield

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

Down syndrome (DS) is one of the most common causes of intellectual disability, owing to trisomy of all or part of chromosome 21. DS is also associated with the development of Alzheimer disease (AD) neuropathology after the age of 40 years. To better clarify the cellular and metabolic pathways that could contribute to the differences in DS brain, in particular those involved in the onset of neurodegeneration, we analyzed the frontal cortex of DS subjects with or without significant AD pathology in comparison with age-matched controls, using a proteomics approach. Proteomics represents an advantageous tool to investigate the molecular mechanisms underlying the disease. From these analyses, we investigated the effects that age, DS, and AD neuropathology could have on protein expression levels. Our results show overlapping and independent molecular pathways (including energy metabolism, oxidative damage, protein synthesis, and autophagy) contributing to DS, to aging, and to the presence of AD pathology in DS. Investigation of pathomechanisms involved in DS with AD may provide putative targets for therapeutic approaches to slow the development of AD.

Original languageEnglish
Pages (from-to)89-95
Number of pages7
JournalFree Radical Biology and Medicine
Volume76
DOIs
StatePublished - Nov 2014

Bibliographical note

Publisher Copyright:
© 2014 Elsevier Inc.

Keywords

  • Alzheimer disease
  • Down syndrome
  • Free radicals
  • Neuropathology
  • Proteomics
  • Trisomy 21

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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