Quantitative proteomics identifies altered O-GlcNAcylation of structural, synaptic and memory-associated proteins in Alzheimer's disease: Brain protein O-GlcNAcylation in Alzheimer's disease

Wang, Sheng; Yang, Feng; Petyuk, Vladislav A.; Shukla, Anil K.; Monroe, Matthew E.; Gritsenko, Marina A.; Rodland, Karin D.; Smith, Richard D.; Qian, Wei-Jun; Gong, Cheng-Xin; Liu, Tao

doi:10.1002/path.4929

Title: Quantitative proteomics identifies altered O-GlcNAcylation of structural, synaptic and memory-associated proteins in Alzheimer's disease: Brain protein O-GlcNAcylation in Alzheimer's disease

Journal Article · Fri Jul 28 00:00:00 EDT 2017 · Journal of Pathology

DOI:https://doi.org/10.1002/path.4929· OSTI ID:1378037

Wang, Sheng ^[1]; Yang, Feng ^[1]; Petyuk, Vladislav A. ^[1]; Shukla, Anil K. ^[1]; Monroe, Matthew E. ^[1]; Gritsenko, Marina A. ^[1]; Rodland, Karin D. ^[1]; Smith, Richard D. ^[1]; Qian, Wei-Jun ^[1]; Gong, Cheng-Xin ^[2];

^[1]

Biological Sciences Division, Pacific Northwest National Laboratory, Richland WA USA
New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York USA

Protein modification by O-linked beta-N-acetylglucosamine (O-GlcNAc) is emerging as an important factor in the pathogenesis of sporadic Alzheimer’s disease. Herein we report the most comprehensive, quantitative proteomics analysis for protein O-GlcNAcylation in post-mortem human brains with and without Alzheimer’s using isobaric tandem mass tags labeling, chemoenzymatic photocleavage enrichment and liquid chromatography coupled to mass spectrometry. A total of 1,850 O-GlcNAc peptides covering 1,094 O-GlcNAcylation sites were identified from 530 proteins in the human brain. 128 O-GlcNAc peptides covering 78 proteins were altered significantly in Alzheimer’s brain as compared to controls (q<0.05). Moreover, alteration of the O-GlcNAc peptide abundance could be attributed more to O-GlcNAcylation level than to protein level changes. The altered O-GlcNAcylated proteins belong to several structural and functional categories, including synaptic proteins, cytoskeleton proteins, and memory-associated proteins. These findings suggest that dysregulation of O-GlcNAcylation of multiple brain proteins may be involved in the development of sporadic Alzheimer’s disease.

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Research Organization:: Pacific Northwest National Lab. (PNNL), Richland, WA (United States). Environmental Molecular Sciences Lab. (EMSL)

Sponsoring Organization:: USDOE

DOE Contract Number:: AC05-76RL01830

OSTI ID:: 1378037

Report Number(s):: PNNL-SA-119241; 48135; 48666; 453040220

Journal Information:: Journal of Pathology, Vol. 243, Issue 1; ISSN 0022-3417

Publisher:: Wiley

Country of Publication:: United States

Language:: English

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