Researchers discovered that ALS, a serious disease affecting nerve and muscle function, shows detectable warning signs in the blood up to 20 years before people develop symptoms. By studying nearly 4,600 healthy people over 30 years, scientists identified five specific proteins that appear to predict who will develop ALS later in life. These proteins are involved in immune system function, muscle health, and metabolism. The findings suggest that ALS doesn’t suddenly appear—instead, it develops slowly over many years with measurable changes happening long before diagnosis. This discovery could eventually help doctors identify at-risk people early and develop treatments to prevent or delay the disease.

The Quick Take

  • What they studied: Can scientists detect ALS before people show any symptoms by looking at proteins in the blood?
  • Who participated: Nearly 4,600 healthy people from five European countries who were followed for up to 30 years. During this time, 172 of them developed ALS. Researchers also tested their findings in two separate groups of people who already had ALS.
  • Key finding: Five specific proteins in the blood can predict ALS diagnosis up to 20 years before symptoms appear. Four of these proteins were confirmed in separate groups of ALS patients, suggesting they’re reliable markers of the disease.
  • What it means for you: This research suggests ALS develops slowly over decades with detectable changes in the blood long before symptoms. While this is early-stage research, it may eventually lead to blood tests that identify people at risk, allowing for earlier treatment. However, having these proteins doesn’t mean someone will definitely develop ALS—more research is needed.

The Research Details

Scientists used a large European health study that tracked healthy people for up to 30 years. They collected blood samples from participants when they were healthy and tested these samples for 7,285 different proteins using advanced technology. When some participants later developed ALS, researchers compared their old blood samples to those who stayed healthy. This allowed them to identify which proteins were present years before ALS diagnosis. To confirm their findings, they tested the results in two separate groups of people who already had ALS, comparing their protein levels to healthy controls.

This approach is powerful because it looks backward in time—researchers had blood samples from before people got sick, which is much better than studying people after they’re already diagnosed. The study examined proteins involved in immune function, muscle health, metabolism, and brain function to understand how ALS develops.

This research design is important because it shows what happens in the body long before ALS symptoms appear. Most previous ALS studies looked at people who already had the disease, making it impossible to know what came first. By studying blood samples collected decades before diagnosis, scientists can identify the earliest changes that lead to ALS. This helps distinguish between changes that cause the disease versus changes that result from having the disease.

This study has several strengths: it followed people for up to 30 years (very long-term), included nearly 4,600 participants, tested thousands of proteins using advanced technology, and confirmed findings in separate groups of ALS patients. However, the study is published as a preprint, meaning it hasn’t yet been reviewed by other scientists for a journal. The number of people who developed ALS (172) is relatively small, which means results need confirmation in larger studies. The research was conducted in Europe, so findings may need testing in other populations.

What the Results Show

Scientists identified five proteins that appeared in blood samples up to 20 years before ALS diagnosis: SECTM1, CA3, THAP4, KLHL41, and SLC26A7. These proteins were found in people who would later develop ALS but were less common in people who stayed healthy. Four of these five proteins (all except SECTM1) were confirmed when researchers tested them in separate groups of people who already had ALS, suggesting they’re reliable markers.

Beyond these five main proteins, researchers found 22 additional proteins that showed promise as early warning signs. These proteins were associated with immune system function, muscle health, metabolism, and digestive processes—suggesting that ALS affects multiple body systems years before symptoms appear.

The study also revealed that certain tissues age faster in people destined to develop ALS. Specifically, the brain, immune system, and muscles showed signs of accelerated aging in blood samples taken before diagnosis. This suggests ALS involves premature aging of these systems rather than a sudden disease onset.

When researchers compared ALS biomarkers to early warning signs of other brain diseases like Parkinson’s and Alzheimer’s, they found that ALS has a largely unique protein signature. This means the early changes in ALS are different from other common brain diseases, which could help doctors distinguish between them.

The research identified several biological pathways involved in early ALS development. Gene analysis showed that immune system activation, muscle protein breakdown, and metabolic dysfunction all appear years before diagnosis. The digestive system also showed early involvement, which hasn’t been emphasized in previous ALS research. Additionally, researchers used artificial intelligence to analyze the proteins and identify potential drug targets—compounds that could theoretically be used to treat ALS if given early enough.

Previous ALS research has focused mainly on people who already have symptoms, making it difficult to understand what starts the disease. This study is the first to systematically examine blood samples from healthy people years before ALS diagnosis, providing unprecedented insight into the disease’s early development. Earlier research suggested ALS involves immune system problems and muscle degeneration, and this study confirms these findings while showing they begin decades before symptoms. The discovery that multiple body systems are involved early on expands our understanding beyond the traditional focus on nerve cells alone.

This study has several important limitations. First, it’s a preprint that hasn’t been peer-reviewed by other scientists yet. Second, only 172 people developed ALS during the 30-year follow-up, which is a relatively small number for identifying rare disease markers. Third, the study was conducted in Europe, so results may not apply equally to other populations with different genetics or environments. Fourth, having these proteins doesn’t mean someone will definitely develop ALS—the study shows association, not certainty. Finally, the study doesn’t prove these proteins cause ALS; they may simply be markers of other underlying processes. More research is needed to understand whether these proteins could be therapeutic targets.

The Bottom Line

Based on this early-stage research, there are no immediate changes people should make. This is fundamental research that helps scientists understand ALS development. However, the findings suggest that future blood tests could identify people at high risk for ALS years before symptoms appear. If confirmed in larger studies, this could enable early intervention strategies. People with a family history of ALS should stay informed about this research, as it may eventually lead to screening options. Healthcare providers should monitor this research as it develops.

This research is most relevant to: people with a family history of ALS, neurologists and ALS specialists, pharmaceutical companies developing ALS treatments, and public health researchers. People without ALS symptoms or family history don’t need to take action based on this study alone. However, the findings may eventually benefit everyone by leading to earlier ALS detection and treatment.

This is very early-stage research. Even if these proteins prove useful for diagnosis, it will likely take 5-10 years of additional studies before blood tests become available to the general public. Any treatments targeting these proteins would require even longer development. People should not expect immediate clinical applications but should view this as an important step toward better ALS prevention and treatment.

Want to Apply This Research?

  • For users with family history of ALS or personal concern: Track any new neurological symptoms (muscle weakness, twitching, speech changes, difficulty swallowing) with dates and severity. Note any changes in energy levels, exercise tolerance, or muscle function. This creates a baseline for discussions with healthcare providers.
  • While waiting for future blood tests, users can: maintain detailed health records including any neurological symptoms, stay informed about ALS research developments, discuss family history with healthcare providers, and maintain overall health through exercise and proper nutrition—all factors that may support nervous system health.
  • Set up quarterly check-ins to review symptom tracking. Create reminders to discuss any concerning changes with a healthcare provider. Follow reputable ALS research organizations for updates on biomarker testing development. For those with family history, consider genetic counseling to understand personal risk factors.

This research is published as a preprint and has not yet been peer-reviewed by other scientists. The findings are preliminary and should not be used for personal medical decisions. Having these proteins does not mean someone will definitely develop ALS. This study identifies associations, not definitive causes. Anyone concerned about ALS risk should consult with a neurologist or healthcare provider. This information is for educational purposes only and should not replace professional medical advice, diagnosis, or treatment.