Lipidomic Analysis Reveals Biomarkers for Alzheimer's Disease

Introduction: Alzheimer's disease (AD) is a leading cause of death in older adults, necessitating early diagnosis for effective management and treatment. Lipidomics, a branch of metabolomics, holds promise as an early diagnostic tool for various diseases, including neurodegenerative conditions. In this study, we investigated the lipidomic profile in the cerebral spinal fluids (CSF) of human subjects with subjective cognitive impairment (SCI), mild cognitive impairment (MCI), and AD. Methodology: One hundred and twenty participants from the Memory Clinic at Karolinska University Hospital, Huddinge, Sweden, provided consent for this study. Lipids were extracted from CSF samples using the Folch's extraction procedure, and LC-MS/MS analysis was conducted using a Xevo TQ equipped with Acquity I class UPLC. Lipid species were quantified as percentages of total phospholipids or based on the abundance of internal standards for free fatty acid analysis. Results: We identified and analyzed 451 lipid species in CSF samples. Notably, several phospholipids (PCs) showed significant differences during AD progression. PC54:12, PC48:12, and PC38:0 ( D) exhibited decreased levels, while PC36:1, PC36: 2, and PC38:3 (E) showed increased levels. Additionally, correlations between cognitive status and lipid mediators, such as PGE2 and PGD2 related to inflammation, and NPD1, LTB4, RVD1, and Maresin1, involved in inflammation resolution, were observed. Conclusion and Discussion: This study emphasizes the critical roles of phospholipids and lipid mediators in human biological fluids, highlighting their potential as key components for detecting and understanding dementia. The identification of lipid mediators in human CSF presents promising therapeutic opportunities and supports their clinical diagnostic utility. Lipidomic analysis offers valuable insights for early diagnosis and targeted therapeutic approaches for AD and other neurodegenerative diseases. Further research in this area could lead to the development of novel biomarkers and treatments to combat the devastating effects of AD.