Exploring Alzheimer's disease biomarkers: A comprehensive lipidomics approach using untargeted LC/MS

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive memory loss, affecting 55 million people worldwide with no cure and limited reliable biomarkers. Lipidomics offers a promising approach for the early detection of lipid-based biomarkers. This study aims to analyze lipid profiles in clinical samples to determine the lipid biomarkers for AD progression.

The objective is to perform a comprehensive lipidome analysis of saliva, plasma, and fecal samples from AD patients. In this study, we performed an untargeted lipidomics approach using high-performance liquid chromatography coupled with linear-ion trap-Orbitrap mass spectrometry to identify lipid biomarkers. The saliva, plasma, and fecal samples were collected from healthy individuals (n=81, 60, 87), mild cognitive impairment (MCI) patients (n=37, 26, 37), and dementia patients (n=6, 4, 4) respectively.

The lipidomic analysis identified 266, 217, and 260 lipid metabolites from five major lipid classes across saliva, plasma, and fecal samples, respectively. In the saliva, fatty acids such as FA 20:4 and FA 22:5 are upregulated in the MCI group and phospholipids such as LPE 20:4, LPE 22:5, and PI (18:0/20:4) were increased with the disease progression and particularly higher in the dementia group. In saliva, triacylglycerols containing medium-chain fatty acids (TG-MCFAs) are decreased in both MCI and dementia groups. Plasma also showed similar changes to that of saliva with increased FA 20:4, FA 22:5, LPE 22:5, LPC 22:5, and LPC 22:6 in MCI and dementia groups. In the fecal samples, TG-MCFAs are upregulated in the MCI group compared to the control, suggesting the possible excretion of these lipids in MCI patients.

This study highlights stage-specific lipid alterations in saliva, plasma, and fecal samples. TG-MCFAs could serve as non-invasive biomarkers for AD progression, offering valuable insights for lipid-based diagnostic tools and advancing AD research, which could be of significant interest to the AOCS phospholipid community.