Common Blood Biomarker Changes Linked to ALS Progression, Study Determines

Changes in commonly tested blood biomarkers in people with amyotrophic lateral sclerosis (ALS) may be associated with faster disease progression and an increased risk of mortality, according to a recent study.

Given the easy access and low cost of these standard blood tests, monitoring such biomarkers over time may help better understand ALS progression and aid in disease prognosis.

The study, “Blood biomarkers and prognosis of amyotrophic lateral sclerosis,” was published in the European Journal of Neurology. 

Blood biomarkers are molecules that can be measured that relate to disease  processes, which can be used to diagnose a condition or predict how a disease will develop (prognosis).

There is ongoing research to identify blood biomarkers associated with ALS. Most often, prognostic biomarkers, measured at the time of diagnosis, are used to predict disease progression and mortality. However, biomarker levels may change over time. 

Studies have examined how changes in biomarker levels were linked to functional decline, but studies investigating biomarker change (before and after diagnosis) and mortality in ALS patients are still needed. 

“To our knowledge, such efforts have rarely been made in identifying novel prognostic indicators for ALS,” the researchers wrote. 

In this study, researchers at the Karolinska Institutet in Sweden analyzed the medical records of 231 men and 168 women newly diagnosed with ALS from 2006 to 2011; their average age was 66. 

The team explored the relationship between biomarkers measured at the time of diagnosis (baseline) and the risk of mortality after diagnosis, and investigated the association between changes in biomarker levels and disease progression and survival. 

Data were collected from eight biochemical blood tests that are used routinely in clinical settings, measured both at baseline and again after diagnosis. Patients were followed until they either left the area, died, or at the study cutoff date. The average follow-up period was 2.36 years. 

The biomarkers measured were glucose, potassium, sodium, calcium, hemoglobin, albumin (a test for liver function) serum creatinine (a marker for kidney health) and C‐reactive protein (CRP, a measure of inflammation). 

Patients with lower-than-median levels of creatinine or albumin measured at baseline had a higher risk of mortality, as well as those with a higher-than-median level of CRP and glucose. No significant relationship was observed for baseline measurements of hemoglobin, potassium, sodium, or calcium.

The analysis of biomarker change over time found patients with the most significant decrease in creatinine after diagnosis had more than double the risk of mortality. The authors said that a “decreasing creatinine level might be a marker of muscle wasting.”

Similar results were seen in those whose albumin levels decreased the most over time. There also was a non-significant trend showing decreasing hemoglobin levels were associated with mortality risk. 

An increase in the inflammatory marker CRP was associated with two times higher risk of mortality. 

“These results provide further evidence for the involvement of altered immune responses and inflammation in ALS, especially in the later phase of disease progression,” the researchers wrote. 

A higher risk also was identified in those whose glucose levels increased the most. 

Finally, the team analyzed biomarker levels in patients who died within one year (fast progression), or one to three years (medium progression), compared to those who survived more than three years after diagnosis (slow progression). 

The greatest decline in creatinine was found in patients with fast and medium progression. Compared to those with slow progression, patients with the most significant decrease in creatinine progressed most rapidly. Although not as significant, a similar pattern was seen for albumin and hemoglobin. 

The highest increase in CRP and glucose was noted during the months preceding death, with the greatest increase found in those in the fast and medium progression groups, compared to the slow progression group. No clear pattern was identified for potassium, sodium, or calcium.

“Altogether, our findings lend support to the idea of monitoring both the baseline levels and the temporal changes of serum creatinine, albumin, CRP, and glucose in the clinical care of ALS patients to better understand disease progression,” the researchers wrote. 

“Given their easy access and low cost, the usefulness of these routinely measured blood biomarkers in clinical practice and clinical trials of ALS warrants further assessment,” they concluded.