Plasma lipidomics showed widespread lipid dysregulation in ALS, with predominantly decreased acylcarnitines, and exploratory analyses suggest that genetic predisposition to adiposity may shape the pattern of lipid metabolic disruption in ALS, although no significant mediation by lipids was detected.
ALS patients showed widespread plasma lipid dysregulation compared with controls.
Acylcarnitines were predominantly decreased in ALS patients.
A three-acylcarnitine panel (C10:0, C12:0 and C18:2) discriminated ALS patients from controls with high accuracy in cross-validation.
Exploratory analyses identified nominal interactions between life-course adiposity polygenic risk scores and disease status on the lipidome, mostly involving acylcarnitines.
No significant mediation effect of lipids between adiposity PRS and ALS risk was detected.
This study measured hundreds of fats (lipids) in blood plasma from 104 people with amyotrophic lateral sclerosis (ALS) and 78 matched healthy people. ALS patients had widespread differences in their lipid profiles, with 78 lipid species clearly altered. Most notably, acylcarnitines, molecules involved in moving fats into cells' energy-producing machinery, were mostly lower in ALS patients. Changes were also seen in other lipid families such as sphingolipids and glycerophospholipids. The researchers also found that a combination of just three acylcarnitines could separate ALS patients from controls very well in internal cross-validation (AUC 0.958). In addition, they examined genetic scores reflecting a person's inherited tendency toward body fat and lean mass across life. Some of these scores appeared to interact with ALS status in how they related to lipid levels, especially acylcarnitines, but these were exploratory, nominal signals. A formal test did not find that lipids explain the link between these genetic scores and ALS risk. This research suggests that ALS involves a distinctive change in energy-related fat metabolism that can be seen in blood, and that inherited tendencies related to body composition may influence this pattern. The findings are from a single study with a modest sample size and need confirmation in independent groups before any use as a diagnostic tool or any conclusions about causes.
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Upload Your LabsZhang L, Zhang L, Zheng Y, Zhuang Z, Tang L, Zheng W, et al.. (2026). Plasma Lipidome Is Dysregulated in Amyotrophic Lateral Sclerosis and Associated With Life-Course Adiposity Polygenic Risk.. Journal of cachexia, sarcopenia and muscle. https://doi.org/10.1002/jcsm.70410