Association of APOE Ε4 Genotype With Lipid Profile in Patients With Alzheimer's Disease

Abstract

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disorder in which genetic susceptibility and disturbances in lipid metabolism contribute to disease onset and progression. The Apolipoprotein E (APOE) ε4 allele has been consistently implicated in late-onset AD, while alterations in circulating lipids, small dense low-density lipoprotein (sdLDL), and lipoprotein-associated phospholipase A₂ (Lp-PLA₂) may further influence neurodegenerative and vascular processes. However, evidence describing their combined relationship in postmenopausal women remains limited.

Objective: To investigate the association between APOE (rs429358) polymorphism, lipid profile, sdLDL, and Lp-PLA₂ in female patients with Alzheimer's disease and cognitively healthy women.

Methods: This hospital-based case-control study enrolled 100 postmenopausal women, including 50 clinically diagnosed Alzheimer's disease patients and 50 age-matched cognitively normal controls. Fasting serum lipid parameters were estimated using standard biochemical methods, plasma Lp-PLA₂ was quantified by ELISA, and sdLDL was calculated using the Sampson equation. APOE (rs429358) polymorphisms were determined by PCR-restriction fragment length polymorphism analysis. Genotype distribution, biochemical parameters, and their associations with Alzheimer's disease were statistically evaluated.

Results: Women with Alzheimer's disease demonstrated significantly higher concentrations of total cholesterol, triglycerides, LDL-C, non-HDL-C, VLDL-C, cholesterol/HDL ratio, sdLDL, and Lp-PLA₂, whereas HDL-C was significantly reduced compared with controls. The T allele and TT genotype of APOE (rs429358) occurred more frequently among Alzheimer's disease patients and showed a strong association with disease risk. Individuals carrying the TT genotype also exhibited a more atherogenic lipid profile, characterized by increased total cholesterol, triglycerides, LDL-C, non-HDL-C, VLDL-C, and sdLDL together with lower HDL-C. These findings indicate that APOE-related lipid dysregulation is closely linked with metabolic and vascular abnormalities in Alzheimer's disease.

Conclusion: The present study highlights a significant relationship between APOE polymorphism and adverse lipid alterations in female patients with Alzheimer's disease. The combined assessment of APOE genotype, lipid profile, sdLDL, and Lp-PLA₂ may improve identification of individuals at increased risk and provide clinically relevant biomarkers for early diagnosis and disease stratification. Larger prospective studies are warranted to validate these findings and clarify their prognostic value.