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

被引:13
作者
Lin, Ching-Yu [1 ,2 ,3 ]
Sheu, Jau-Jiuan [4 ,5 ]
Tsai, I-Shih [1 ]
Wang, Sen-Te [6 ,7 ]
Yang, Li-Yu [1 ]
Hsu, I-Uen [1 ,8 ]
Chang, Hui-Wen [9 ]
Lee, Horng-Mo [1 ,2 ]
Kao, Shu-Huei [1 ,2 ]
Lee, Ching-Kuo [10 ]
Chen, Chien-Ho [1 ,2 ]
Lin, Yung-Feng [1 ,2 ]
机构
[1] Taipei Med Univ, Coll Med Sci & Technol, Sch Med Lab Sci & Biotechnol, Taipei 110, Taiwan
[2] Taipei Med Univ, Coll Med Sci & Technol, PhD Program Med Biotechnol, Taipei 110, Taiwan
[3] Natl Ilan Univ, Dept Biotechnol & Anim Sci, Ilan 260, Taiwan
[4] Taipei Med Univ Hosp, Dept Neurol, Taipei 110, Taiwan
[5] Taipei Med Univ, Coll Med, Sch Med, Dept Neurol, Taipei 110, Taiwan
[6] Taipei Med Univ, Coll Med, Sch Med, Dept Family Med, Taipei 110, Taiwan
[7] Taipei Med Univ Hosp, Hlth Management Ctr, Taipei 110, Taiwan
[8] Univ Michigan, Dept Mol Cellular & Dev Biol, Ann Arbor, MI 48109 USA
[9] Taipei Med Univ Hosp, Dept Lab Med, Taipei 110, Taiwan
[10] Taipei Med Univ, Coll Pharm, Sch Pharm, Taipei 110, Taiwan
关键词
Alzheimer's disease; Post-translational modification; Advanced glycation end products; ApoA1; CEL; Autoimmunity; GLYCATION END-PRODUCTS; AMYLOID PRECURSOR PROTEIN; BETA; PLASMA; METHYLGLYOXAL; BIOMARKERS;
D O I
10.1016/j.clinbiochem.2018.04.009
中图分类号
R446 [实验室诊断]; R-33 [实验医学、医学实验];
学科分类号
1001 ;
摘要
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: N epsilon-(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.
引用
收藏
页码:75 / 82
页数:8
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