Amyotrophic lateral sclerosis (ALS) is characterized by progressive loss of 
upper and lower motor neurons leading to muscle paralysis and death. While a 
link between dysregulated lipid metabolism and ALS has been proposed, lipidome 
alterations involved in disease progression are still understudied. Using a 
rodent model of ALS overexpressing mutant human Cu/Zn-superoxide dismutase gene 
(SOD1-G93A), we performed a comparative lipidomic analysis in motor cortex and 
spinal cord tissues of SOD1-G93A and WT rats at asymptomatic (~70 days) and 
symptomatic stages (~120 days). Interestingly, lipidome alterations in motor 
cortex were mostly related to age than ALS. In contrast, drastic changes were 
observed in spinal cord of SOD1-G93A 120d group, including decreased levels of 
cardiolipin and a 6-fold increase in several cholesteryl esters linked to 
polyunsaturated fatty acids. Consistent with previous studies, our findings 
suggest abnormal mitochondria in motor neurons and lipid droplets accumulation 
in aberrant astrocytes. Although the mechanism leading to cholesteryl esters 
accumulation remains to be established, we postulate a hypothetical model based 
on neuroprotection of polyunsaturated fatty acids into lipid droplets in 
response to increased oxidative stress. Implicated in the pathology of other 
neurodegenerative diseases, cholesteryl esters appear as attractive targets for 
further investigations.