Exploring differences in circulating metabolites of females and males with Alzheimer’s disease

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that leads to cognitive and functional decline and primarily affects the elderly population. Metabolic alterations, particularly in the amino acid and fatty acid pathways, are increasingly being recognized in AD. However, the role of sex in these metabolic changes remains insufficiently understood, despite evidence suggesting that AD may manifest more strongly in females. This study investigated sex-specific metabolic patterns in AD by analyzing routine and non-routine hematological tests, including amino acids and fatty acid profiles. The results showed that certain metabolites such as citrulline and alanine were frequently altered in patients with AD. Notably, docosahexaenoic acid, dihomo-gamma-linolenic acid, and gamma-linolenic acid levels were exclusively elevated in female patients. Additionally, females exhibited significantly lower Aβ42 and higher gamma-linolenic acid levels than males, with the trend becoming more pronounced during the early stages of the disease. Despite these differences, most metabolic markers did not show significant sex-based variation. These findings suggest that while some sex-specific metabolic differences exist in AD, a larger cohort is needed to confirm these patterns and fully understand the influence of sex on AD-related metabolic changes.