Higher ‘Good’ Cholesterol Levels Appear to Lower Risk of ALS

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by Margarida Maia PhD |

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Certain blood biomarkers of lipid, or fat, metabolism — typically measured to determine a person’s risk of cardiovascular disease — appear to protect against developing amyotrophic lateral sclerosis (ALS), a study of more than 500,000 adults reported.

Specifically, researchers found that people with higher levels of high density lipoprotein (HDL) — the “good” cholesterol — and apolipoprotein A1 (ApoA1; a component of HDL) had a significantly lower risk of ALS.

“Such markers might help to target population screening for ALS,” the researchers wrote.

The study, “Higher blood high density lipoprotein and apolipoprotein A1 levels are associated with reduced risk of developing amyotrophic lateral sclerosis,” was published in the Journal of Neurology, Neurosurgery & Psychiatry.

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A number of studies suggest a link between ALS and lipid metabolism, with patients showing changes in their lipid metabolites as much as a decade before their diagnosis.

These molecules might be biomarkers for early disease detection, but most studies examining metabolic factors as biomarkers of ALS focused on specific cases, and as such had limitations that could affect broader conclusions.

A team of researchers in the U.K. conducted a large study to examine a number of metabolic markers and determine their association with the risk of ALS.

Records came from the UK Biobank, a database containing information on over half a million of people ages 39 to 72. Participants underwent an initial assessment between March 2006 and October 2010, and were followed for a median of 11.9 years.

Analyses covered data on 502, 409 people, including 343 who were diagnosed with ALS during the follow-up period. This accounted for 5.85 new cases per 100,000 people per year.

After controlling for age and sex, the researchers found that higher blood levels of HDL and ApoA1 were associated with a 16% to 17% lower risk of ALS. In turn, a higher ratio of total cholesterol to HDL was associated with a 17% greater risk of ALS. (Total cholesterol, the fat-like substance in cells, includes HDL and low-density lipoprotein or LDL, the “bad” cholesterol.)

Models that accounted for multiple factors beyond age and sex also known to impact lipid metabolism — including vascular diseases, smoking, use of statins (cholesterol-lowering medications), body mass index, and creatinine (a marker of kidney function) — were then used in analyses.

Again, higher HDL and ApoA1 levels associated with a reduced risk of ALS.

“The persistence of these findings in models controlling for statin use, smoking and vascular disease indicates that the association of lipid levels and ALS is not attributable to a confounding association between lipids, ALS and these factors,” the researchers wrote.

A person’s risk of ALS, however, rose with higher levels of LDL and a component of this molecule, called apolipoprotein B (ApoB).

Older age, coronary artery disease (caused by a buildup of cholesterol in the arteries that supply blood to the heart), and cerebrovascular disease (a disease of the blood vessels that supply the brain) were also associated with an increased risk of ALS.

An analysis of metabolic markers in the years before an ALS diagnosis also found that blood levels of LDL and ApoB sustainably decreased until the time of diagnosis in those who went on to develop ALS, while remaining stable in a matched group of people serving as controls.

HDL and ApoA1 levels remained stable in both patients and controls over time, although they were consistently lower in patients than in controls.

“Understanding the molecular basis for these changes will inform … biomarker development and therapeutic targeting,” the researchers concluded. “Such markers might help to target population screening for ALS and also build confidence in future trials of preventative therapy.”