title: Mitochondrial Proteome Changes Correlating with β-Amyloid Accumulation.
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.
authors.affiliation: MTA-ELTE NAP B Laboratory of Molecular and Systems Neurobiology, Hungarian Academy of Sciences and Eötvös Loránd University, Budapest, Hungary. katvolgyi@gmail.com.|Laboratory of Proteomics, Eötvös Loránd University, Budapest, Hungary. katvolgyi@gmail.com.
authors.forename: Katalin
authors.initials: K
authors.lastname: Völgyi
authors.affiliation: Laboratory of Proteomics, Eötvös Loránd University, Budapest, Hungary.
authors.forename: Krisztina
authors.initials: K
authors.lastname: Háden
authors.affiliation: Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Budapest, Hungary.
authors.forename: Viktor
authors.initials: V
authors.lastname: Kis
authors.affiliation: Laboratory of Proteomics, Eötvös Loránd University, Budapest, Hungary.|MTA-TTK NAP B MS Neuroproteomics Research Group, Research Center for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: Péter
authors.initials: P
authors.lastname: Gulyássy
authors.affiliation: Laboratory of Proteomics, Eötvös Loránd University, Budapest, Hungary.
authors.forename: Kata
authors.initials: K
authors.lastname: Badics
authors.affiliation: Laboratory of Proteomics, Eötvös Loránd University, Budapest, Hungary.|MTA-ELTE NAP B Neuroimmunology Research Group, Hungarian Academy of Sciences and Eötvös Loránd University, Budapest, Hungary.
authors.forename: Balázs András
authors.initials: BA
authors.lastname: Györffy
authors.affiliation: Laboratory of Proteomics, Eötvös Loránd University, Budapest, Hungary.
authors.forename: Attila
authors.initials: A
authors.lastname: Simor
authors.affiliation: Medical Chemistry Department, University of Szeged, Szeged, Hungary.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Szabó
authors.affiliation: Medical Chemistry Department, University of Szeged, Szeged, Hungary.
authors.forename: Tamás
authors.initials: T
authors.lastname: Janáky
authors.affiliation: MTA-TTK NAP B MS Neuroproteomics Research Group, Research Center for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Drahos
authors.affiliation: MTA-ELTE NAP B Laboratory of Molecular and Systems Neurobiology, Hungarian Academy of Sciences and Eötvös Loránd University, Budapest, Hungary.
authors.forename: Árpád
authors.initials: Á
authors.lastname: Dobolyi
authors.affiliation: Medical Chemistry Department, University of Szeged, Szeged, Hungary.
authors.forename: Botond
authors.initials: B
authors.lastname: Penke
authors.affiliation: Laboratory of Proteomics, Eötvös Loránd University, Budapest, Hungary.|MTA-TTK NAP B MS Neuroproteomics Research Group, Research Center for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: Gábor
authors.initials: G
authors.lastname: Juhász
authors.affiliation: Laboratory of Proteomics, Eötvös Loránd University, Budapest, Hungary.|Department of Physiology and Neurobiology, Eötvös Loránd University, Budapest, Hungary.
authors.forename: Katalin Adrienna
authors.initials: KA
authors.lastname: Kékesi
mesh_terms: D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D020543:Proteome / Q000235:genetics / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D020543:Proteome
keywords: APP/PS1 mouse model; Alzheimer’s disease (AD); Non-synaptic mitochondria; Synaptic mitochondria; β-Amyloid (Aβ)