iTRAQ analysis of complex proteome alterations in 3xTgAD Alzheimer's mice: Understanding the interface between physiology and disease

Bronwen Martin, Randall Brenneman, Kevin G. Becker, Marjan Gucek, Robert N. Cole, Stuart Maudsley

Research output: Contribution to journalArticlepeer-review

Abstract

Alzheimer's disease (AD) is characterized by progressive cognitive impairment associated with accumulation of amyloid β-peptide, synaptic degeneration and the death of neurons in the hippocampus, and temporal, parietal and frontal lobes of the cerebral cortex. Analysis of postmortem brain tissue from AD patients can provide information on molecular alterations present at the end of the disease process, but cannot discriminate between changes that are specifically involved in AD versus those that are simply a consequence of neuronal degeneration. Animal models of AD provide the oppurtunity to elucidate the molecular changes that occur in brain cells as the disease process is initiated and progress. To this end, we used the 3xTgAD mouse model of AD to gain insight into the complex alterations in proteins that occur in the hippocampus and cortex in AD. The 3xTgAD mice express mutant presenillin-1, amyloid precursor protien and tau, and exhibit AD-like amyloid and tau pathology in the hippocampus and cortex, and associated cognitive impairment. Using the iTRAQ stable-isotope-based quantitative proteomic technique, we performed an in-depth proteomic analysis of hippocampal and cortical tissue from 16 month old 3xTgAD and non-transgenic control mice. We found that the most important groups of significantly altered protiens included those involved in synaptic plasticity, neurite outgrowth and microtubule dynamics. Our findings have elucidated some of the complex proteome changes that occur in a mouse model of AD, which could potentially illuminated novel therapeutic aveneus for the treatment of AD and other neurodegenerative disorders.

Original languageEnglish (US)
Article numbere2750
JournalPloS one
Volume3
Issue number7
DOIs
StatePublished - Jul 23 2008

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Fingerprint Dive into the research topics of 'iTRAQ analysis of complex proteome alterations in 3xTgAD Alzheimer's mice: Understanding the interface between physiology and disease'. Together they form a unique fingerprint.

Cite this