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Elevated blood levels of the Cystatin C protein are significantly associated with faster disease progression and shorter survival in people with <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS), according to a study in China.
The protein may serve as a biomarker to predict disease outcomes in people with ALS and identify those who need more invasive strategies earlier in the disease course, the findings suggest.
Cystatin C “has the potential to be a widely used and reproducible biomarker for monitoring disease progression in ALS,” the researchers wrote in “<a href="https://link.springer.com/article/10.1007/s10072-023-06957-9">Serum Cystatin C is a potential biomarker for predicting amyotrophic lateral sclerosis survival</a>,” which was published in <a href="https://www.springer.com/journal/10072">Neurological Sciences</a>.
ALS is caused by the damage and death of motor neurons, the nerve cells that control voluntary movements. This causes a loss of control of muscle movements, and patients progressively become less able to go about their daily lives without assistance.
About 90% of cases are <a href="https://alsnewstoday.com/sporadic-als/">sporadic</a>, meaning they occur spontaneously. The remaining 10%, which run in families, are called <a href="https://alsnewstoday.com/forms-of-als-familial-als/">familial ALS</a>. Although many studies have focused on the genetic causes of familial ALS, less is known about the mechanisms leading to sporadic ALS.
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<h3>Connecting Cystatin C levels to disease progression, survival</h3>
Cystatin C is a small protein used to monitor kidney problems and has also been associated with disease severity in ALS. Yet, studies examining the link between Cystatin C and ALS survival and progression have yielded conflicting results, leading researchers in China to assess the potential biomarker&#8217;s levels in 356 patients with sporadic ALS at their hospital between 2016-2019 to shed more light on this association.
Most participants (57%) were men, with a mean age at disease onset of 53.3 and a mean interval between symptom onset and <a href="https://alsnewstoday.com/als-diagnosis/">diagnosis</a> of 13.8 months. They were followed by neurologists via phone or in-person interviews every six months until January 2022. During that time, 226 patients (63.5%) died and 26 (7.3%) were lost to follow-up.
On average, the levels of Cystatin C in serum (the liquid portion of blood) at diagnosis were 1 mg/L. Based on that average, patients were divided into two groups: those with levels of 1 mg/L or higher and those with levels below the average.
The high Cystatin C group had a significantly higher proportion of men (71.5% vs. 44.5%) and of patients with limb-onset disease (89.1% vs. 55.5%), a form of the disease in which the first <a href="https://alsnewstoday.com/als-symptoms/">symptoms of muscle weakness</a> appear in the limbs. This group was also significantly older at the onset of the disease (57.7 vs. 49.5%).
The participants in the high and low Cystatin C groups also had differences in clinical measures. In fact, the high group had significantly less disease severity, as measured with the ALS Functional Rating Scale-Revised (ALSFRS-R), but a faster rate of disease progression.
The higher the Cystatin C levels, the less severe the disease was, but the faster it progressed, according to statistical analyses that looked at Cystatin C levels as a continuous variable.
This suggests “serum [Cystatin C] may be a useful indicator for assessing disease severity, [and that] patients with higher [Cystatin C] levels might have faster disease progression,&#8221; the researchers wrote.
The median survival time for all the patients was 42 months (around 3.5 years). However, consistent with the faster rate of disease progression in those with high Cystatin C levels, this group also had a significantly shorter survival compared with the group with low levels (38 vs. 48 months). In a multivariate analysis, which took into account potential confounding factors such as age and sex, low serum Cystatin C remained associated with a longer survival time with ALS.
Other factors significantly associated with longer survival included a lower age at disease onset, limb onset, a longer time between the appearance of the first symptoms and diagnosis, a slower disease progression rate, and being male.
“Our study found that serum [Cystatin C] seems to be associated with ALS survival and serum [Cystatin C] may be an independent predictor of ALS survival,” the researchers said.

Tag: Cystatin C

Cystatin C may be biomarker to predict survival, disease progression