Mitochondrial Proteome Changes Correlating with β-Amyloid Accumulation

Katalin Völgyi, Krisztina Háden, Viktor Kis, Péter Gulyássy, Kata Badics, Balázs András Györffy, Attila Simor, Zoltán Szabó, Tamás Janáky, László Drahos, Árpád Dobolyi, Botond Penke, Gábor Juhász, Katalin Adrienna Kékesi

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Alzheimer’s disease (AD) is a multifactorial disease of wide clinical heterogenity. Overproduction of amyloid precursor protein (APP) and accumulation of β-amyloid (Aβ) and tau proteins are important hallmarks of AD. The identification of early pathomechanisms of AD is critically important for discovery of early diagnosis markers. Decreased brain metabolism is one of the earliest clinical symptoms of AD that indicate mitochondrial dysfunction in the brain. We performed the first comprehensive study integrating synaptic and non-synaptic mitochondrial proteome analysis (two-dimensional differential gel electrophoresis (2D-DIGE) and mass spectrometry) in correlation with Aβ progression in APP/PS1 mice (3, 6, and 9 months of age). We identified changes of 60 mitochondrial proteins that reflect the progressive effect of APP overproduction and Aβ accumulation on mitochondrial processes. Most of the significantly affected proteins play role in the mitochondrial electron transport chain, citric acid cycle, oxidative stress, or apoptosis. Altered expression levels of Htra2 and Ethe1, which showed parallel changes in different age groups, were confirmed also by Western blot. The common regulator bioinformatical analysis suggests the regulatory role of tumor necrosis factor (TNF) in Aβ-mediated mitochondrial protein changes. Our results are in accordance with the previous postmortem human brain proteomic studies in AD in the case of many proteins. Our results could open a new path of research aiming early mitochondrial molecular mechanisms of Aβ accumulation as a prodromal stage of human AD.

Original languageEnglish
Pages (from-to)2060-2078
Number of pages19
JournalMolecular Neurobiology
Volume54
Issue number3
DOIs
Publication statusPublished - Apr 1 2017

Keywords

  • APP/PS1 mouse model
  • Alzheimer’s disease (AD)
  • Non-synaptic mitochondria
  • Synaptic mitochondria
  • β-Amyloid (Aβ)

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

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