Amyotrophic lateral sclerosis (ALS) is a multifactorial and complex fatal 
degenerative disorder. A number of pathological mechanisms that lead to motor 
neuron death have been identified, although there are many unknowns in the 
disease aetiology of ALS. Alterations in lipid metabolism are well documented in 
the progression of ALS, both at the systemic level and in the spinal cord of 
mouse models and ALS patients. The origin of these lipid alterations remains 
unclear. This study aims to identify early lipid metabolic pathways altered 
before systemic metabolic symptoms in the spinal cord of mouse models of ALS. To 
do this, we performed a transcriptomic analysis of the spinal cord of SOD1G93A 
mice at an early disease stage, followed by a robust transcriptomic 
meta-analysis using publicly available RNA-seq data from the spinal cord of SOD1 
mice at early and late symptomatic disease stages. The meta-analyses identified 
few lipid metabolic pathways dysregulated early that were exacerbated at 
symptomatic stages; mainly cholesterol biosynthesis, ceramide catabolism, and 
eicosanoid synthesis pathways. We present an insight into the pathological 
mechanisms in ALS, confirming that lipid metabolic alterations are 
transcriptionally dysregulated and are central to ALS aetiology, opening new 
options for the treatment of these devastating conditions.