What Causes ALS — What We Know and What Remains Unknown

The Short Answer

Most people with ALS have no family history of the disease, and scientists do not yet know what causes it in those cases. About 10 percent of ALS cases run in families and are caused by inherited genetic mutations. For both inherited and non-inherited forms, the disease involves the death of motor neurons — the nerve cells that control voluntary movement — but the exact mechanism that triggers this death remains unclear. Researchers have identified several genetic variants and environmental factors that may increase risk, but no single cause has been proven to start the disease in most people.

This does not mean ALS is random. It means that the combination of factors leading to motor neuron death likely differs from person to person, and identifying those combinations is what researchers are working to understand.

Key Takeaways

Sporadic ALS, which accounts for about 90 percent of cases, has no known single cause, though genetic and environmental factors likely play a role.
Familial ALS, inherited through families, is caused by mutations in specific genes, most commonly SOD1, C9orf72, and FUS.
Motor neurons gradually die in ALS, leading to muscle weakness and paralysis, but why this happens in most cases is still being studied.
Possible risk factors include age, sex, military service, and exposure to certain environmental toxins, though none has been proven to cause ALS on its own.

Sporadic ALS: The Majority of Cases Without a Clear Cause

About 90 percent of ALS cases are sporadic, meaning they appear without a family history of the disease. In these cases, the cause is unknown. This does not mean the disease is random or unpredictable — it means that the combination of factors that led to motor neuron death in one person may be different from the combination in another.

Researchers believe sporadic ALS likely results from a mix of genetic susceptibility and environmental exposure. A person might carry genetic variants that make their motor neurons more vulnerable, and then an environmental trigger — or simply aging — tips the balance toward disease. Because the disease takes years to develop, it is difficult to identify what that trigger was by the time symptoms appear. This is why sporadic ALS is harder to study than inherited forms: there is no single gene to track, and no clear moment when the disease began. Researchers instead look for patterns across large groups of people to find factors that appear more often in those with ALS than in those without it.

Familial ALS: Inherited Genetic Mutations

When ALS runs in families, it is caused by a mutation in a specific gene that a parent passes to their children. The most common genes involved are SOD1, C9orf72, and FUS. Each of these genes normally produces a protein that helps motor neurons function. When the gene is mutated, the protein either does not work correctly or becomes toxic to the cell.

Familial ALS typically follows an autosomal dominant pattern, meaning a person needs to inherit only one mutated copy of the gene — from either parent — to develop the disease. If one parent carries the mutation, each child has a 50 percent chance of inheriting it. Not everyone who inherits the mutation will develop ALS, and the age at which symptoms start can vary even within the same family. Identifying the specific gene mutation in a family is valuable because it narrows the focus of research and sometimes opens the door to targeted treatments. For example, antisense oligonucleotide therapy has been developed for people with C9orf72 mutations, and other gene-targeted approaches are in development.

How Motor Neurons Die in ALS

Regardless of whether ALS is inherited or sporadic, the disease involves the progressive death of motor neurons in the brain and spinal cord. These neurons normally send signals that tell muscles to contract. As they die, muscles weaken, waste away, and eventually become paralyzed.

Scientists have observed several processes that may contribute to motor neuron death: abnormal protein accumulation inside cells, inflammation, problems with how cells handle energy, and damage to the structures that transport materials within the cell. In inherited ALS, the mutated protein often plays a direct role in one or more of these processes. In sporadic ALS, it is less clear which of these processes is most important, and it may differ from person to person. The fact that motor neurons are selectively affected — while other nerve cells remain relatively healthy — suggests that motor neurons have some unique vulnerability. Researchers are still working to understand what makes them different and why they are targeted in ALS.

Environmental and Lifestyle Factors Under Investigation

Several environmental exposures and lifestyle factors have been studied as possible risk factors for ALS. These include military service, exposure to pesticides or heavy metals, smoking, and head trauma. People with ALS are somewhat more likely to report these exposures than people without ALS, but none has been proven to cause the disease.

The challenge is that ALS develops over many years, often decades. By the time someone is diagnosed, it is difficult to remember or document exactly what they were exposed to and when. Additionally, many people with these exposures never develop ALS, and some people with ALS have no known exposure to any identified risk factor. Military service is one of the more consistent associations found in research, though the reason is unclear. It may relate to specific exposures during service, or to factors like physical stress or infection. Research into environmental causes continues, but so far no single exposure has been identified as necessary or sufficient to cause ALS.

Age, Sex, and Other Demographic Patterns

ALS typically begins in people aged 55 to 75, though it can occur at any age. Men are diagnosed slightly more often than women, though the reason for this difference is not fully understood. It may reflect a true difference in disease risk, or it may relate to differences in how symptoms are recognized or reported.

Familial ALS often starts earlier than sporadic ALS, sometimes in people in their 30s or 40s. The age of onset can vary significantly even within families carrying the same mutation, suggesting that other genetic or environmental factors modify when the disease appears. These demographic patterns help researchers identify who to study and what questions to ask, but they do not explain the underlying cause of ALS. Age itself is a risk factor for many neurodegenerative diseases, possibly because motor neurons accumulate damage over time or because protective mechanisms decline with age.

What Research Is Ongoing

Current research focuses on understanding the cellular and molecular processes that lead to motor neuron death, identifying new genetic variants involved in sporadic ALS, and testing whether environmental factors interact with genetic susceptibility. Large studies are also underway to collect detailed information about people's exposures, medical history, and genetics in hopes of finding patterns that point toward cause.

Animal models and laboratory studies of human motor neurons have revealed many processes that go wrong in ALS, but translating these findings into treatments has proven difficult. This suggests that ALS may not have a single cause that, once fixed, stops the disease — it may instead involve multiple overlapping processes that vary from person to person. Understanding these variations is central to why the cause of most ALS cases remains unknown.

Frequently Asked Questions

Is ALS always inherited?

No. About 90 percent of ALS cases are sporadic, meaning they do not run in families. Only about 10 percent of cases are familial ALS, caused by an inherited genetic mutation. Even in families with ALS, not everyone who carries the mutation develops the disease.

Can you catch ALS from someone else?

No. ALS is not contagious. It is not spread through contact, air, food, or water. The disease involves changes in a person's own nerve cells and cannot be transmitted to another person.

If my parent has ALS, will I definitely get it?

Not necessarily. If your parent has familial ALS caused by an inherited mutation, you have a 50 percent chance of inheriting that mutation. However, inheriting the mutation does not may provide you will develop ALS — some people with the mutation never show symptoms. If your parent has sporadic ALS with no family history, your risk is not significantly higher than the general population.

Can environmental exposure alone cause ALS?

No single environmental exposure has been proven to cause ALS on its own. Some exposures are more common in people with ALS than in those without, but many people with those exposures never develop the disease. ALS likely requires a combination of factors, which may differ from person to person.

Why do scientists still not know what causes most ALS?

ALS develops over many years, making it hard to identify what triggered it. The disease likely involves multiple overlapping processes rather than one simple cause. Additionally, the factors that matter may be different in different people, which makes finding a universal cause difficult.

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