Elevated IgM against Nε-(Carboxyethyl)lysine-modified Apolipoprotein A1 peptide 141-147 in Taiwanese with Alzheimer's disease

Ching-Yu Lin; Jau-Jiuan Sheu; I-Shih Tsai; Sen-Te Wang; Li-Yu Yang; I-Uen Hsu; Hui-Wen Chang; Horng-Mo Lee; Shu-Huei Kao; Ching-Kuo Lee; Chien-Ho Chen; Yung-Feng Lin

doi:10.1016/j.clinbiochem.2018.04.009

Elevated IgM against Nε-(Carboxyethyl)lysine-modified Apolipoprotein A1 peptide 141-147 in Taiwanese with Alzheimer's disease

Clin Biochem. 2018 Jun:56:75-82. doi: 10.1016/j.clinbiochem.2018.04.009. Epub 2018 Apr 20.

Authors

Ching-Yu Lin¹, Jau-Jiuan Sheu², I-Shih Tsai³, Sen-Te Wang⁴, Li-Yu Yang³, I-Uen Hsu⁵, Hui-Wen Chang⁶, Horng-Mo Lee⁷, Shu-Huei Kao⁷, Ching-Kuo Lee⁸, Chien-Ho Chen⁹, Yung-Feng Lin¹⁰

Affiliations

¹ School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan; Ph.D. Program in Medical Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan; Department of Biotechnology and Animal Science, National Ilan University, Ilan 260, Taiwan.
² Department of Neurology, Taipei Medical University Hospital, Taipei 110, Taiwan; Department of Neurology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.
³ School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan.
⁴ Department of Family Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan; Health Management Center, Taipei Medical University Hospital, Taipei 110, Taiwan.
⁵ School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan; Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
⁶ Department of Laboratory Medicine, Taipei Medical University Hospital, Taipei 110, Taiwan.
⁷ School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan; Ph.D. Program in Medical Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan.
⁸ School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 110, Taiwan.
⁹ School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan; Ph.D. Program in Medical Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan. Electronic address: chenchho@tmu.edu.tw.
¹⁰ School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan; Ph.D. Program in Medical Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan. Electronic address: yflin@tmu.edu.tw.

PMID: 29680706
DOI: 10.1016/j.clinbiochem.2018.04.009

Abstract

Objective: Advanced glycation end products (AGEs) are involved in the pathogenesis of Alzheimer's disease (AD). Specific AGEs and related autoantibodies may be early AD markers. Apolipoprotein A1 (ApoA1) and its post-translational modifications (PTMs) are associated with neurodegeneration and thus selected to test the hypothesis.

Methods: Serum samples from totally 64 AD or health control (HC) Taiwanese were analyzed. ApoA1 was isolated from the serum and examined through LC-MS/MS and PTM analyses. A specific AGE and its autoantibodies were determined using Western blotting or ELISA.

Results: Nε-(Carboxyethyl)lysine (CEL) modification, a kind of AGEs, was identified on ApoA1 peptide ¹⁴¹-QKVEPLR-¹⁴⁷ (ApoA1^141-147) from AD serum. Total CEL adducts and autoantibodies against CEL on ApoA1^141-147 were significantly increased in AD samples. The area under the receiver operating characteristic curve was 0.965 for anti-CEL-ApoA1^141-147 IgM. Mini Mental State Examination scores of the AD patients were positively correlated with anti-CEL-ApoA1^141-147 IgM, suggesting that the IgM level is high in early AD pathology and decreased with disease progression.

Conclusion: CEL modification was increased on AD serum proteins including ApoA1, leading to an elevated anti-CEL IgM in early disease state. Both CEL and anti-CEL IgM may serve as AD biomarkers.

Keywords: Advanced glycation end products; Alzheimer's disease; ApoA1; Autoimmunity; CEL; Post-translational modification.

MeSH terms

Aged
Aged, 80 and over
Alzheimer Disease / blood*
Alzheimer Disease / diagnosis
Alzheimer Disease / immunology
Alzheimer Disease / metabolism
Antibody Specificity
Apolipoprotein A-I / antagonists & inhibitors*
Apolipoprotein A-I / blood
Apolipoprotein A-I / chemistry
Autoantibodies / blood*
Autoimmunity
Biomarkers / blood
Case-Control Studies
Enzyme-Linked Immunosorbent Assay
Female
Glycation End Products, Advanced / antagonists & inhibitors*
Glycation End Products, Advanced / blood
Glycation End Products, Advanced / chemistry
Humans
Immunoglobulin M / analysis*
Lysine / analogs & derivatives
Lysine / blood
Lysine / chemistry
Male
Peptide Fragments / antagonists & inhibitors
Peptide Fragments / blood
Peptide Fragments / chemistry
Protein Processing, Post-Translational*
Psychiatric Status Rating Scales
ROC Curve
Taiwan
Up-Regulation*

Substances

APOA1 protein, human
Apolipoprotein A-I
Autoantibodies
Biomarkers
Glycation End Products, Advanced
Immunoglobulin M
N(6)-carboxyethyllysine
Peptide Fragments
Lysine