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Levels of the TDP-43 protein in spinal fluid show promise as biomarkers for <a class="editor-rtfLink" href="https://alsnewstoday.com/what-is-als/" target="_blank" rel="noopener">amyotrophic lateral sclerosis</a> (ALS) and may aid in diagnosing the neurological disease, according to a new review of several published studies.
That review discovered that these protein levels are increased in the cerebrospinal fluid (CSF) — the liquid that surrounds the brain and spinal cord — of patients as compared with people without ALS.
This finding suggests that TDP-43 levels may be a biomarker to help diagnose the disease. However, the scientists noted that the analysis included a small number of studies and participants, and stressed that more research is needed to validate this hypothesis.
“CSF TDP-43 could represent a biomarker of ALS, but further studies are mandatory before drawing conclusions,” the team wrote.
The study, “<a class="editor-rtfLink" href="https://www.mdpi.com/2075-4418/13/3/416" target="_blank" rel="noopener">The Role of TAR DNA Binding Protein 43 (TDP-43) as a CandiDate Biomarker of Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-Analysis</a>,” was published in <a class="editor-rtfLink" href="https://www.mdpi.com/journal/diagnostics" target="_blank" rel="noopener">Diagnostics</a>.
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<h3>Searching for new biomarkers for use in diagnosis</h3>
<a class="editor-rtfLink" href="https://alsnewstoday.com/causes-of-als/" target="_blank" rel="noopener">ALS is caused</a> by the progressive death of motor neurons, the nerve cells in the brain and spinal cord that control voluntary movements. This gives rise to a range of <a href="https://alsnewstoday.com/symptoms-of-als/">symptoms</a>, such as muscle stiffness and weakness, that also are signs of other diseases.
Thus, confirming an <a href="https://alsnewstoday.com/als-diagnosis/">ALS diagnosis</a> remains a challenge for clinicians, who need to conduct multiple tests to rule out other conditions and track the progression of symptoms before attributing them to ALS. As a result, it generally takes <a href="https://www.sciencedirect.com/science/article/pii/S0022510X20303919">about 10-16 months</a> from the onset of symptoms to an ALS diagnosis.
Identifying biomarkers that reflect disease mechanisms has been a main focus of ALS research in recent years. These biomarkers could help distinguish patients with ALS from those with other distinct neurological conditions, helping to shorten the diagnostic journey. Such ALS biomarkers also might aid in tracking disease progression and responses to treatment.
 TDP-43 is a protein abundantly expressed in the brain and spinal cord. It is normally located in the cell nucleus, where it regulates the first step of protein production from a gene, but can shuttle between this compartment and the cytoplasm — the fluid surrounding the nucleus. 
In ALS, however, TDP-43 accumulates and forms toxic clumps in the cytoplasm of motor neurons, causing their dysfunction. This buildup is found in approximately 97% of ALS patients — even in those who do not have mutations in the gene coding for TDP-43. Indeed, it now is recognized as a hallmark of ALS.
But while studies support the role of this protein in ALS development and progression, its function “as a biomarker of ALS is controversial,” the researchers wrote.
To learn more, researchers in Italy now conducted an analysis of studies published up to April 2022, with available measurements of TDP-43 levels in both ALS patients and those without the disorder, who served as controls.
A total of seven studies, involving 452 participants — 254 ALS patients and 198 controls — were eligible for the analysis. Some studies used healthy individuals as controls, but controls in most studies were patients with neurological diseases that should not influence TDP-43 levels, such as <a href="https://multiplesclerosisnewstoday.com/multiple-sclerosis-overview/">multiple sclerosis</a>.
A meta-analysis — a statistical analysis combining results from all studies — revealed that TDP-43 levels in the cerebrospinal fluid were significantly increased in ALS patients compared with controls.
[quote align=&#8221;center&#8221;]The findings of this meta-analysis encourage further studies to validate the possible role of TDP-43 as a biomarker of ALS.[/quote]
Some studies also evaluated TDP-43 in the blood, but the results were inconsistent, possibly due to differences in the methods used to measure the protein, the team noted.
Only a few studies further investigated the diagnostic potential of CSF TDP-43 in ALS — but all reported good diagnostic performance.
Together, the findings suggest that CSF TDP-43 may be a potential biomarker of ALS, but “much effort is needed before introducing it in clinical practice,” the researchers wrote, noting, &#8220;A significant limitation of most studies is the small sample size.&#8221;
“The findings of this meta-analysis encourage further studies to validate the possible role of TDP-43 as a biomarker of ALS,” the team concluded.

Tag: cerebrospinal fluid

TDP-43 protein levels show promise as ALS biomarker: Review