Identification of a New Plasma Biomarker of Alzheimer Disease using Metabolomics Technology

Abstract
In order to precisely quantify variations in desmosterol between normal controls and Alzheimers Disease (AD) patients, we established an analytical method to measure desmosterol and cholesterol concentration using LC/APCI-MS system that allowed separating 5 endogenous main isomers and interfering peaks. The analysis revealed that Desmosterol, a cholesterol precursor, was found to be decreased in AD plasma vs healthy elderly controls plasma. Using this LC-based method, we discovered that desmosterol and desmosterol/ cholesterol ratio are significantly decreased in AD patients, although such changes could not be observed using previous GC methods. Those changes were not observed in samples from Parkinsons disease (PD) and schizophrenia patients samples, suggesting the specific association of desmosterol with AD and or with cognitive decline. Finally the validation of this assay using 109 clinical samples confirmed the decrease of desmosterol in AD patients as well as a change in desmosterol/ cholesterol ratio in AD patients plasma. In addition, the decrease of desmosterol was somewhat more significant in female patients. Although larger sample populations will be needed to confirm this diagnostic marker sensitivity, our studies demonstrate a sensitive and accurate method of detecting plasma desmosterol concentration and suggest that plasma desmosterol could be become a powerful new specific biomarker for the early and easy AD diagnosis.

The article is published online in the Journal of Lipid Research and is free to access.