Serum levels of 4-hydroxynonenal adducts and responding autoantibodies correlate with the pathogenesis from hyperglycemia to Alzheimer's disease

Monika Renuka Sanotra, Wen Chung Huang, Simon Silver, Ching Yu Lin, Tsuei Chuan Chang, Doan Phuong Quy Nguyen, Ching Kuo Lee, Shu Huei Kao, Jonathan Chang-Cheng Shieh, Yung Feng Lin

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Objective: Hyperglycemia leads to lipid peroxidation, producing 4-hydroxynonenal (HNE) adducts which correlate with the production of amyloid-beta (Aβ), one of the hallmarks of Alzheimer's disease (AD). This study is to investigate the interactions of Aβ, HNE adducts and responding autoantibodies during the pathogenesis from hyperglycemia to AD. Methods: A total of 239 Taiwanese serum samples from a healthy control group and patients with hyperglycemia, and AD with and without hyperglycemia were analyzed. Aβ was immunoprecipitated from randomly pooled serum in each group and immunoblotted. Synthetic Aβ1-16 and Aβ17-28 peptides were modified with HNE in vitro and verified with LC-MS/MS. The levels of Aβ, HNE adducts, and autoantibody isotypes IgG and IgM against either native or HNE-modified Aβ were determined with ELISA. The diagnostic power of potential biomarkers was evaluated. Results: Increased fasting glucose and decreased high-density-lipoprotein cholesterol in AD groups indicated abnormal metabolism in the pathogenesis progression from hyperglycemia to AD. Indeed, serum Aβ, HNE adducts and most of the autoantibodies recognizing either native or HNE-modified Aβ were increased in the diseased groups. However, HNE adducts had better diagnostic performances than Aβ for both hyperglycemia and AD. Additionally, HNE-Aβ peptide levels were increased, and the responding autoantibodies (most notably IgM) were decreased in hyperglycemic AD group compared to the hyperglycemia only group, suggesting an immunity disturbance in the pathogenesis progression from hyperglycemia to AD. Conclusion: Hyperglycemia increases the level of HNE adducts which may be neutralized by responding autoantibodies. Depletion of these autoantibodies promotes AD-like pathogenesis. Thus, levels of a patient's HNE adducts and associated responding autoantibodies are potential biomarkers for AD with diabetes.

Original languageEnglish
Pages (from-to)26-34
Number of pages9
JournalClinical Biochemistry
Volume101
DOIs
Publication statusPublished - Mar 2022

Keywords

  • 4-Hydroxynonenal (HNE)
  • Alzheimer's disease (AD)
  • Amyloid-beta (Aβ)
  • Autoantibody
  • Hyperglycemia
  • Post-translational modification

ASJC Scopus subject areas

  • Clinical Biochemistry

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