CE(20:4) and CE(22:5) cholesteryl ester levels are elevated in the plasma of Alzheimer’s disease patients with ε3/ε4 genotype

Aim: This study investigates the association between ApoE genotype, plasma cholesteryl ester (CE) levels, and Alzheimer’s disease (AD) status, with a focus on CE(20:4) and CE(22:5) levels as potential indicators of lipid metabolism alterations in AD patients. Methods: Publicly available metabolomics data (DOI: 10.3233/JAD-215448) from 94 AD patients and 62 controls aged 55 and older were re-analyzed. CE levels were examined using non-parametric tests due to the non-normal overall data distribution. Comparisons were stratified by ApoE genotypes (ε3/ε3 and ε3/ε4). Results: Significant increases in CE(20:4) and CE(22:5) levels were observed in AD patients with the ApoE ε3/ε4 genotype compared to controls (p-values 0.0387 and 0.0348, respectively). No significant differences were found for other CEs or among ε3/ε3 carriers (except for sex). Overlap between CE levels in AD and control groups limits their potential as diagnostic biomarkers but underscores their role in lipid dysregulation in AD pathophysiology. Conclusions: Elevated CE(20:4) and CE(22:5) levels in ε3/ε4 AD patients highlight lipid metabolism alterations associated with ApoE genotype. While not providing standalone biomarkers, these findings offer insights into AD-related lipid dysregulation and warrant further investigation in high-risk ε4/ε4 carriers and therapeutic targeting of lipid metabolism.