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

Research output: Contribution to journalArticle

4 Citations (Scopus)

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 (ApoA1141–147) from AD serum. Total CEL adducts and autoantibodies against CEL on ApoA1141–147 were significantly increased in AD samples. The area under the receiver operating characteristic curve was 0.965 for anti-CEL-ApoA1141–147 IgM. Mini Mental State Examination scores of the AD patients were positively correlated with anti-CEL-ApoA1141–147 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.

Original languageEnglish
Pages (from-to)75-82
JournalClinical Biochemistry
DOIs
Publication statusPublished - Jun 2018

Fingerprint

Apolipoproteins
Lysine
Immunoglobulin M
Alzheimer Disease
Peptides
Apolipoprotein A-I
Autoantibodies
Post Translational Protein Processing
Serum
Advanced Glycosylation End Products
ROC Curve
Biomarkers
Disease Progression
Pathology
Blood Proteins
Western Blotting
Enzyme-Linked Immunosorbent Assay
Health

Keywords

  • Advanced glycation end products
  • Alzheimer's disease
  • ApoA1
  • Autoimmunity
  • CEL
  • Post-translational modification

ASJC Scopus subject areas

  • Clinical Biochemistry

Cite this

@article{53e8c4450a024f50a9915fb92e3b414d,
title = "Elevated IgM against Nε-(Carboxyethyl)lysine-modified Apolipoprotein A1 peptide 141–147 in Taiwanese with Alzheimer's disease",
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 (ApoA1141–147) from AD serum. Total CEL adducts and autoantibodies against CEL on ApoA1141–147 were significantly increased in AD samples. The area under the receiver operating characteristic curve was 0.965 for anti-CEL-ApoA1141–147 IgM. Mini Mental State Examination scores of the AD patients were positively correlated with anti-CEL-ApoA1141–147 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",
author = "Lin, {Ching Yu} and Sheu, {Jau Jiuan} and Tsai, {I. Shih} and Wang, {Sen Te} and Yang, {Li Yu} and Hsu, {I. Uen} and Chang, {Hui Wen} and Lee, {Horng Mo} and Kao, {Shu Huei} and Lee, {Ching Kuo} and Chen, {Chien Ho} and Lin, {Yung Feng}",
year = "2018",
month = "6",
doi = "10.1016/j.clinbiochem.2018.04.009",
language = "English",
pages = "75--82",
journal = "Clinical Biochemistry",
issn = "0009-9120",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Elevated IgM against Nε-(Carboxyethyl)lysine-modified Apolipoprotein A1 peptide 141–147 in Taiwanese with Alzheimer's disease

AU - Lin, Ching Yu

AU - Sheu, Jau Jiuan

AU - Tsai, I. Shih

AU - Wang, Sen Te

AU - Yang, Li Yu

AU - Hsu, I. Uen

AU - Chang, Hui Wen

AU - Lee, Horng Mo

AU - Kao, Shu Huei

AU - Lee, Ching Kuo

AU - Chen, Chien Ho

AU - Lin, Yung Feng

PY - 2018/6

Y1 - 2018/6

N2 - 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 (ApoA1141–147) from AD serum. Total CEL adducts and autoantibodies against CEL on ApoA1141–147 were significantly increased in AD samples. The area under the receiver operating characteristic curve was 0.965 for anti-CEL-ApoA1141–147 IgM. Mini Mental State Examination scores of the AD patients were positively correlated with anti-CEL-ApoA1141–147 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.

AB - 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 (ApoA1141–147) from AD serum. Total CEL adducts and autoantibodies against CEL on ApoA1141–147 were significantly increased in AD samples. The area under the receiver operating characteristic curve was 0.965 for anti-CEL-ApoA1141–147 IgM. Mini Mental State Examination scores of the AD patients were positively correlated with anti-CEL-ApoA1141–147 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.

KW - Advanced glycation end products

KW - Alzheimer's disease

KW - ApoA1

KW - Autoimmunity

KW - CEL

KW - Post-translational modification

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U2 - 10.1016/j.clinbiochem.2018.04.009

DO - 10.1016/j.clinbiochem.2018.04.009

M3 - Article

SP - 75

EP - 82

JO - Clinical Biochemistry

JF - Clinical Biochemistry

SN - 0009-9120

ER -