Liu, Yuan, et al. “Isotopic N, N-dimethyl leucine tags for absolute quantification of clusterin and apolipoprotein E in Alzheimer’s disease.” Journal of Proteomics 257 (2022): 104507. https://doi.org/10.1016/j.jprot.2022.104507

Abstract

Alzheimer’s disease (AD) is the most common form of dementia and one of the leading causes of death in the United States. In the past decades, extensive efforts have been devoted to biomarker discovery for early diagnosis and treatment of AD. Herein, this study aims to quantify clusterin (CLU) and apolipoprotein E (APOE) in blood samples from AD patients and evaluate these two proteins as potential biomarkers in AD diagnosis. In-house synthesized 5-plex isotopic N,N-dimethyl leucine (iDiLeu) tags were used to label target peptide standards at different concentrations to construct standard curves. Our study revealed that the levels of CLU and APOE exhibited clear differences in male vs. female AD groups but not in male vs. female non-AD groups. In contrast, the levels of serum CLU and APOE did not show statistically significant differences in the AD groups and non-AD groups. Principal component analysis (PCA) with CLU and APOE showed some separation between the AD and non-AD participants. Significance: Dissecting CLU and APOE heterogeneity in AD pathogenesis may therefore facilitate delineating the pathological relevance for sex-related pathways, leading to personalized medicine in the future. Collectively, this study introduces a cost-effective absolute quantitative proteomics strategy for target protein quantitation and lays the foundation for future investigation of CLU and APOE as potential biomarkers for AD.