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Longitudinal study of differential protein expression in an Alzheimer's mouse model lacking inducible nitric oxide synthase.

Publication ,  Journal Article
Hoos, MD; Richardson, BM; Foster, MW; Everhart, A; Thompson, JW; Moseley, MA; Colton, CA
Published in: J Proteome Res
October 4, 2013

Alzheimer's disease (AD) is a complex neurodegenerative process that involves altered brain immune, neuronal and metabolic functions. Understanding the underlying mechanisms has relied on mouse models that mimic components of AD pathology. We used gel-free, label-free LC-MS/MS to quantify protein and phosphopeptide levels in brains of APPSwDI/NOS2-/- (CVN-AD) mice. CVN-AD mice show a full spectrum of AD-like pathology, including amyloid deposition, hyperphosphorylated and aggregated tau, and neuronal loss that worsens with age. Tryptic digests, with or without phosphopeptide enrichment on an automated titanium dioxide LC system, were separated by online two-dimensional LC and analyzed on a Waters Synapt G2 HDMS, yielding relative expression for >950 proteins and >1100 phosphopeptides. Among differentially expressed proteins were known markers found in humans with AD, including GFAP and C1Q. Phosphorylation of connexin 43, not previously described in AD, was increased at 42 weeks, consistent with dysregulation of gap junctions and activation of astrocytes. Additional alterations in phosphoproteins suggests dysregulation of mitochondria, synaptic transmission, vesicle trafficking, and innate immune pathways. These data validate the CVN-AD mouse model of AD, identify novel disease and age-related changes in the brain during disease progression, and demonstrate the utility of integrating unbiased and phosphoproteomics for understanding disease processes in AD.

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Published In

J Proteome Res

DOI

EISSN

1535-3907

Publication Date

October 4, 2013

Volume

12

Issue

10

Start / End Page

4462 / 4477

Location

United States

Related Subject Headings

  • tau Proteins
  • Tandem Mass Spectrometry
  • Receptors, Complement
  • Proteome
  • Protein Processing, Post-Translational
  • Protein Biosynthesis
  • Phosphorylation
  • Phosphopeptides
  • Nitric Oxide Synthase Type II
  • Molecular Sequence Data
 

Citation

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Hoos, M. D., Richardson, B. M., Foster, M. W., Everhart, A., Thompson, J. W., Moseley, M. A., & Colton, C. A. (2013). Longitudinal study of differential protein expression in an Alzheimer's mouse model lacking inducible nitric oxide synthase. J Proteome Res, 12(10), 4462–4477. https://doi.org/10.1021/pr4005103
Hoos, Michael D., Brenna M. Richardson, Matthew W. Foster, Angela Everhart, J Will Thompson, M Arthur Moseley, and Carol A. Colton. “Longitudinal study of differential protein expression in an Alzheimer's mouse model lacking inducible nitric oxide synthase.J Proteome Res 12, no. 10 (October 4, 2013): 4462–77. https://doi.org/10.1021/pr4005103.
Hoos MD, Richardson BM, Foster MW, Everhart A, Thompson JW, Moseley MA, et al. Longitudinal study of differential protein expression in an Alzheimer's mouse model lacking inducible nitric oxide synthase. J Proteome Res. 2013 Oct 4;12(10):4462–77.
Hoos, Michael D., et al. “Longitudinal study of differential protein expression in an Alzheimer's mouse model lacking inducible nitric oxide synthase.J Proteome Res, vol. 12, no. 10, Oct. 2013, pp. 4462–77. Pubmed, doi:10.1021/pr4005103.
Hoos MD, Richardson BM, Foster MW, Everhart A, Thompson JW, Moseley MA, Colton CA. Longitudinal study of differential protein expression in an Alzheimer's mouse model lacking inducible nitric oxide synthase. J Proteome Res. 2013 Oct 4;12(10):4462–4477.
Journal cover image

Published In

J Proteome Res

DOI

EISSN

1535-3907

Publication Date

October 4, 2013

Volume

12

Issue

10

Start / End Page

4462 / 4477

Location

United States

Related Subject Headings

  • tau Proteins
  • Tandem Mass Spectrometry
  • Receptors, Complement
  • Proteome
  • Protein Processing, Post-Translational
  • Protein Biosynthesis
  • Phosphorylation
  • Phosphopeptides
  • Nitric Oxide Synthase Type II
  • Molecular Sequence Data