Subtype‑specific associations between serum lipid profiles and disease severity in patients with amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a heterogeneous neurodegenerative disorder. Notably, the differences in lipid metabolism between bulbar‑ and limb‑onset subtypes of ALS remain unclear, particularly in non‑Western populations. The present study investigated serum lipid profiles in a Chinese cohort of patients with ALS to explore their associations with disease severity and clinical subtypes. A retrospective, cross‑sectional study was conducted, involving 158 patients with ALS and 62 matched healthy controls. Serum lipid parameters, including total cholesterol (TC), triglycerides (TG), high‑density lipoprotein (HDL), low‑density lipoprotein (LDL), small dense LDL cholesterol (sdLDL‑c), apolipoprotein A‑1 (ApoA1), apolipoprotein B (ApoB) and the TG/HDL ratio, were compared between the groups. Correlation analyses and multivariable linear regression models incorporating phenotype x lipid interaction terms were conducted after adjusting for age, sex, body mass index and disease duration. Patients with ALS exhibited significantly higher TC, TG, LDL, sdLDL‑c, ApoA1, ApoB and TG/HDL ratios than controls. Subtype‑specific analyses revealed different associations; in bulbar‑onset ALS, higher sdLDL‑c and TG/HDL ratios were associated with better functional status, whereas higher HDL and ApoA1 levels were negatively correlated with functional status. By contrast, in limb‑onset ALS, higher sdLDL‑c and ApoB levels were associated with worse function. Interaction analyses confirmed significant phenotype modification for sdLDL‑c, TG/HDL ratio, HDL and ApoA1. These results suggest that lipid‑severity relationships in ALS vary by subtype, indicating metabolic heterogeneity across phenotypes and supporting the potential of specific lipid parameters as exploratory markers for disease monitoring.