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

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.