Serafini Sara, Angiolillo Antonella, Ferretti Gabriella, Viviani Giulia, Matrone Carmela, Di Costanzo Alfonso
Unit of Pharmacology, Department of Neuroscience, Faculty of Medicine, University of Naples Federico II, Naples, Italy.
Department of Medicine and Health Sciences, "V.Tiberio", Centre for Research and Training in Medicine of Aging, University of Molise, Campobasso, Italy.
J Cereb Blood Flow Metab. 2025 May 16:271678X251340513. doi: 10.1177/0271678X251340513.
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.
阿尔茨海默病（AD）是一种进行性神经退行性疾病，会导致认知和功能衰退，主要影响老年人群体。代谢改变，尤其是氨基酸和脂肪酸代谢途径的改变，在AD中越来越受到关注。然而，尽管有证据表明AD在女性中可能表现得更为明显，但性别在这些代谢变化中的作用仍未得到充分理解。本研究通过分析常规和非常规血液学检测，包括氨基酸和脂肪酸谱，调查了AD中的性别特异性代谢模式。结果表明，某些代谢物，如瓜氨酸和丙氨酸，在AD患者中经常发生改变。值得注意的是，二十二碳六烯酸、二高-γ-亚麻酸和γ-亚麻酸水平仅在女性患者中升高。此外，女性的Aβ42水平显著低于男性，γ-亚麻酸水平高于男性，且在疾病早期这种趋势更为明显。尽管存在这些差异，但大多数代谢标志物并未表现出显著的性别差异。这些发现表明，虽然AD中存在一些性别特异性的代谢差异，但需要更大规模的队列研究来证实这些模式，并充分了解性别对AD相关代谢变化的影响。
