Journal Article
. 2013 Apr; 36(2):321-34.
doi: 10.3233/JAD-130311.

Quantitative proteomic analysis of the hippocampus in the 5XFAD mouse model at early stages of Alzheimer's disease pathology

Ingie Hong 1 Taewook Kang  Yongcheol Yoo  Royun Park  Junuk Lee  Sukwon Lee  Jeongyeon Kim  Boemjong Song  Se-Young Kim  Minho Moon  Ki Na Yun  Jin Young Kim  Inhee Mook-Jung  Young Mok Park  Sukwoo Choi  
Affiliations
  • PMID: 23603400
  •     17 citations

Abstract

Alzheimer's disease (AD) is characterized by progressive memory loss accompanied by synaptic and neuronal degeneration. Although research has shown that substantial neurodegeneration occurs even during the early stages of AD, the detailed mechanisms of AD pathogenesis are largely unknown because of difficulties in diagnosis and limitations of the analytical methods. The 5XFAD mouse model harbors five early-onset familial AD (FAD) mutations and displays substantial amyloid plaques and neurodegeneration. Here, we use quantitative mass spectrometry to identify proteome-wide changes in the 5XFAD mouse hippocampus during the early stages of AD pathology. A subset of the results was validated with immunoblotting. We found that the 5XFAD mice display higher expression of ApoE, ApoJ (clusterin), and nicastrin, three important proteins in AD that are known to participate in amyloid-β processing and clearance, as well as the neurological damage/glial marker protein GFAP and other proteins. A large subset of the proteins that were up- or downregulated in 5XFAD brains have been implicated in neurological disorders and cardiovascular disease, suggesting an association between cardiovascular disease and AD. Common upstream regulator analysis of upregulated proteins suggested that the XBP1, NRF2, and p53 transcriptional pathways were activated, as was IGF-1R signaling. Protein interactome analysis revealed an interconnected network of regulated proteins, with two major sub-networks centered on AβPP processing membrane complexes and mitochondrial proteins. Together with a recent study on the transcriptome of 5XFAD mice, our study allows a comprehensive understanding of the molecular events occurring in 5XFAD mice during the early stages of AD pathology.

New insight into neurodegeneration: the role of proteomics.
Ramavati Pal, Guido Alves, Jan Petter Larsen, Simon Geir Møller.
Mol Neurobiol, 2013 Dec 11; 49(3). PMID: 24323427
Review.
Temporal gene profiling of the 5XFAD transgenic mouse model highlights the importance of microglial activation in Alzheimer's disease.
Véréna Landel, Kévin Baranger, +5 authors, François Féron.
Mol Neurodegener, 2014 Sep 13; 9. PMID: 25213090    Free PMC article.
Altered theta oscillations and aberrant cortical excitatory activity in the 5XFAD model of Alzheimer's disease.
Magdalena Elisabeth Siwek, Ralf Müller, +7 authors, Anna Papazoglou.
Neural Plast, 2015 Apr 30; 2015. PMID: 25922768    Free PMC article.
Proteome-wide characterization of signalling interactions in the hippocampal CA4/DG subfield of patients with Alzheimer's disease.
Jae Ho Kim, Julien Franck, +10 authors, Young Mok Park.
Sci Rep, 2015 Jun 11; 5. PMID: 26059363    Free PMC article.
Histone H3 Ser57 and Thr58 phosphorylation in the brain of 5XFAD mice.
Kyle W Anderson, Natalia Mast, Irina A Pikuleva, Illarion V Turko.
FEBS Open Bio, 2015 Jul 23; 5. PMID: 26199864    Free PMC article.
Effects of BACE1 haploinsufficiency on APP processing and Aβ concentrations in male and female 5XFAD Alzheimer mice at different disease stages.
L Devi, M Ohno.
Neuroscience, 2015 Sep 01; 307. PMID: 26314636    Free PMC article.
Hippocampal proteomics defines pathways associated with memory decline and resilience in normal aging and Alzheimer's disease mouse models.
Sarah M Neuner, Lynda A Wilmott, +2 authors, Catherine C Kaczorowski.
Behav Brain Res, 2016 Jun 07; 322(Pt B). PMID: 27265785    Free PMC article.
Aβ42 oligomers modulate β-secretase through an XBP-1s-dependent pathway involving HRD1.
Yannis Gerakis, Julie Dunys, Charlotte Bauer, Fréderic Checler.
Sci Rep, 2016 Nov 18; 6. PMID: 27853315    Free PMC article.
Plant-based foods containing cell wall polysaccharides rich in specific active monosaccharides protect against myocardial injury in rat myocardial infarction models.
Sun Ha Lim, Yaesil Kim, +4 authors, Jongwon Lee.
Sci Rep, 2016 Dec 09; 6. PMID: 27929093    Free PMC article.
Hippocampal Proteomic Analysis Reveals Distinct Pathway Deregulation Profiles at Early and Late Stages in a Rat Model of Alzheimer's-Like Amyloid Pathology.
Sonia Do Carmo, Gogce Crynen, +5 authors, A Claudio Cuello.
Mol Neurobiol, 2017 May 16; 55(4). PMID: 28502044
Myeloperoxidase Deficiency Inhibits Cognitive Decline in the 5XFAD Mouse Model of Alzheimer's Disease.
Rotem Volkman, Tali Ben-Zur, +2 authors, Daniel Offen.
Front Neurosci, 2019 Oct 16; 13. PMID: 31611761    Free PMC article.
Deep proteome profiling of the hippocampus in the 5XFAD mouse model reveals biological process alterations and a novel biomarker of Alzheimer's disease.
Dong Kyu Kim, Dohyun Han, +8 authors, Inhee Mook-Jung.
Exp Mol Med, 2019 Nov 16; 51(11). PMID: 31727875    Free PMC article.
Centella Asiatica Improves Memory and Promotes Antioxidative Signaling in 5XFAD Mice.
Donald G Matthews, Maya Caruso, +6 authors, Amala Soumyanath.
Antioxidants (Basel), 2019 Dec 11; 8(12). PMID: 31817977    Free PMC article.
Brain proteomics links oxidative stress with metabolic and cellular stress response proteins in behavioural alteration of Alzheimer's disease model rats.
Mohammad Azizur Rahman, Shahdat Hossain, Noorlidah Abdullah, Norhaniza Aminudin.
AIMS Neurosci, 2020 Apr 29; 6(4). PMID: 32341985    Free PMC article.
Systems-based proteomics to resolve the biology of Alzheimer's disease beyond amyloid and tau.
Sruti Rayaprolu, Lenora Higginbotham, +5 authors, Nicholas T Seyfried.
Neuropsychopharmacology, 2020 Sep 09; 46(1). PMID: 32898852    Free PMC article.
Review.
Clusterin secreted from astrocyte promotes excitatory synaptic transmission and ameliorates Alzheimer's disease neuropathology.
Fading Chen, Dan B Swartzlander, +3 authors, Hui Zheng.
Mol Neurodegener, 2021 Feb 02; 16(1). PMID: 33517893    Free PMC article.
Hippocampal disruptions of synaptic and astrocyte metabolism are primary events of early amyloid pathology in the 5xFAD mouse model of Alzheimer's disease.
Jens V Andersen, Niels H Skotte, +15 authors, Helle S Waagepetersen.
Cell Death Dis, 2021 Oct 18; 12(11). PMID: 34657143    Free PMC article.