Higher HDL and apolipoprotein A1 levels associated with a reduced risk of ALS

According to research published in the Journal of Neurology, Neurosurgery, and Psychiatry, lipid metabolism is linked to the risk of developing amyotrophic lateral sclerosis (ALS).

Premorbid metabolic profiles can provide insights into relevant biomarkers such as high-density lipoprotein (HDL) and apolipoprotein A1, which can be used as targets for preventive therapies or for ALS screening.

Since factors that contribute to the development of ALS are largely unknown, the researchers in this large-scale cohort study attempted to examine a number of metabolic parameters for the risk of a later diagnosis of ALS in over half a million people who were admitted to the UK biobank .

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Data from 502,409 people with ALS were prospectively studied, analyzing ALS events 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 rated for their self-reported physical activity and body mass index. Individuals with a baseline ALS diagnosis were excluded from the sample.

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

Of 502,409 participants, 343 were diagnosed with ALS during follow-up. Hazard models showed that an increase in HDL (hazard ratio [HR] 0.84; 95% CI, 0.73-0.96; P = 0.010) and apolipoprotein A1 (HR 0.83; 95% CI, 0.72-0.94; P = 0.005) were independently associated with a reduced risk of developing ALS. However, an increase in the total cholesterol-HDL ratio was associated with an increased risk of developing ALS (HR 1.17; 95% CI 1.05-1.31; P = 0.006). In combined models with multiple metabolic markers, higher HDL and apolipoprotein A1 levels were associated with a lower risk of ALS; higher LDL or apolipoprotein B were associated with an increased risk of ALS. In addition, in all models, coronary artery disease, cerebrovascular disease, and age were significantly associated with a higher risk of ALS.

Study restrictions included a specific UK population who did not necessarily reflect the general population and potential misidentification of ALS cases, which can lead to biased estimates.

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

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

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


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

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