A characteristic N-glycopeptide signature associated with diabetic cognitive impairment identified in a longitudinal cohort study

Yuri Miura, Hiroki Tsumoto, Yukie Masui, Hiroki Inagaki, Madoka Ogawa, Yuta Ideno, Kyojiro Kawakami, Keitaro Umezawa, Mai Kabayama, Yuya Akagi, Hiroshi Akasaka, Koichi Yamamoto, Hiromi Rakugi, Tatsuro Ishizaki, Yasumichi Arai, Kazunori Ikebe, Kei Kamide, Yasuyuki Gondo, Tamao Endo

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)


Background: Identifying a biomarker for the decline in cognitive function in patients with diabetes is important. Therefore, we aimed to identify the N-glycopeptides on plasma proteins associated with diabetic cognitive impairment in participants in a longitudinal study using N-glycoproteomics. Methods: We used samples from the 3-year SONIC (Septuagenarians, Octogenarians, Nonagenarians Investigation with Centenarians) longitudinal cohort study of older Japanese people in the general population. First, we placed the participants with diabetes into two groups: those that did or did not have cognitive decline over a 6-year period. Next, their plasma protein profiles were compared between baseline and the 6-year time point using two-dimensional fluorescence difference gel electrophoresis. Finally, an N-glycoproteomic study of the focused proteins was performed using an enrichment technique and liquid chromatography-tandem mass spectrometry. Results: Approximately 500 N-glycopeptides, derived from 18 proteins, were identified in each sample, from among which we identified the N-glycopeptides that were associated with diabetic cognitive impairment using multivariate analysis. We found that N-glycopeptides with sialylated tri- or tetra-antennary glycans on alpha-2-macroglobulin, clusterin, serum paraoxonase/arylesterase 1, and haptoglobin were less abundant, whereas 3-sialylated tri-antennary N-glycopeptides on serotransferrin were more abundant. Conclusion: N-glycopeptides with sialylated multi-antennary glycans comprise a characteristic signature associated with diabetic cognitive impairment. General significance: The characterized N-glycopeptides represent potential biomarker candidates for diabetic cognitive impairment.

Original languageEnglish
Article number130316
JournalBiochimica et Biophysica Acta - General Subjects
Issue number4
Publication statusPublished - 2023 Apr


  • Cognitive impairment
  • Diabetes
  • Liquid chromatography-tandem mass spectrometry
  • Longitudinal cohort study
  • N-glycoproteomics
  • Proteomics

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology


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