Higher HDL and Apolipoprotein A1 Levels Tied to Reduced ALS Risk

HDL-C test
HDL-C test
Researchers shared their findings on the relationship between metabolic factors, like blood markers of lipid and carbohydrate metabolism, and the risk of developing amyotrophic lateral sclerosis.

Lipid metabolism is associated with the risk of developing amyotrophic lateral sclerosis (ALS), according to study results published in the Journal of Neurology, Neurosurgery, and Psychiatry.

Premorbid metabolic profiles can provide insight into relevant biomarkers including high-density lipoprotein (HDL) and apolipoprotein A1 that may be used as targets for preventative therapies or for ALS screening.

Since factors contributing to the development of ALS are largely unknown, the researchers of this large-scale cohort study sought to examine a range of metabolic parameters on the risk of developing a subsequent ALS diagnosis in over half a million individuals enrolled in the UK Biobank.

Data from 502,409 individuals with ALS were examined prospectively, in which incident ALS cases were analyzed in relation to baseline levels of previously established metabolic biomarkers: blood HDL and low-density lipoprotein (LDL); total cholesterol; total cholesterol to HDL ratio; apolipoproteins A1 and B; triglycerides; HbA1c; and creatinine levels. Participants were also evaluated for self-reported physical activity and body mass index. Individuals with an ALS diagnosis at baseline were left out of the sample.

Researchers performed Cox proportional hazard modeling and controlled for potential confounding variables, including age, gender, statin use, smoking, and cardiovascular and cerebrovascular disease.

Of 502,409 participants, 343 obtained an ALS diagnosis during follow-up. Hazard models indicated that a rise in HDL (hazard ratio [HR] 0.84; 95% CI, 0.73-0.96; P =.010) and apolipoprotein A1 (HR 0.83; 95% CI, 0.72-0.94; P =.005) levels were independently associated with a reduced risk of developing ALS. However, a rise in total cholesterol to HDL ratio was associated with an increased risk of developing ALS (HR 1.17; 95% CI, 1.05-1.31; P =.006). In combined models incorporating multiple metabolic markers, higher levels of HDL and apolipoprotein A1 were associated with lower ALS risk; higher LDL or apolipoprotein B were associated with increased ALS risk. In addition, for all models, coronary artery disease, cerebrovascular disease, and age were significantly associated with higher ALS risk.

Study limitations included a specific UK population that does not necessarily reflect the general population and potential misidentification of ALS cases, which may lead to biased estimates.

Higher baseline levels of the metabolic markers HDL and apolipoprotein A1 — with correspondingly lower total cholesterol to HDL ratio — were associated with a reduced risk for ALS diagnosis during follow up.

Researchers suggest future studies elucidate the mechanism of HDL and apolipoprotein A1 in the pathogenesis of ALS.

“Understanding the molecular basis for these changes will inform presymptomatic biomarker development and therapeutic targeting,” they concluded.


Thompson AG, Talbot K, Turner MR. Higher blood high density lipoprotein and apolipoprotein A1 levels are associated with reduced risk of developing amyotrophic lateral sclerosisJ Neurol Neurosurg Psychiatry. Published online: September 13, 2021. doi:10.1136/jnnp-2021-327133