Causes and Risk Factors of Amyotrophic Lateral Sclerosis (ALS)

Amyotrophic lateral sclerosis (ALS) is considered an idiopathic condition, meaning there is no known trigger for the nerve degeneration that produces its symptoms.

Some weakly associated risk factors include family history and environmental exposures. But most people who have these risk factors don’t develop ALS, and most people who have ALS do not have any ALS risk factors.

This article will discuss possible causes and risk factors for amyotrophic lateral sclerosis, including processes that lead to nerve damage, genetics, and lifestyle risk factors.

Common Causes 

There are some causes associated with ALS, but most are not well established. In fact, 90% of the time, people who develop ALS do not have an identifiable risk factor. 

The only established risk factors for ALS are:

• Older age 
• Being identified as male at birth 
• A family history of ALS 

This condition is considered a motor neuron disease. The motor neurons in the spinal cord play a role in controlling voluntary muscle movement. With ALS, the motor neurons are affected along the length of the spinal cord, on both the right and left sides. 

Specifically, ALS causes degeneration of motor neurons in the anterior horns and lateral columns of the spinal cord. The anterior horns are located toward the front of the spinal cord, and the lateral columns are located at the sides.

Eventually, the spinal motor neuron loss also leads to the degeneration of neurons in the motor cortex, which is an area of the brain that controls voluntary muscle movements.

Nerve Cell Damage

The process that causes motor neurons to become damaged in ALS is not known. Changes in motor neurons that may point to possible types or methods of damage have been identified in research studies.

These include:

• Oxidative damage: This is a type of damage that can affect most cells in the body, and it regularly occurs in moderation. Oxidative damage is caused by normal metabolic changes in the body, but it can also be excessive, causing severe and irreparable damage.
• Defects in axonal transport: The nerve axons are long structures of nerves that play many roles, including sending nerve messages and providing nutrients for nerve function and survival.
• Mitochondrial dysfunction: The mitochondria are structures found in all human cells that produce energy for the cell. Some evidence suggests that mitochondria of the motor neurons may be impaired in ALS.
  

Immune System

The exact trigger for motor neuron damage in ALS is not known, but research shows that inflammatory damage is involved in the process. One of the characteristics of ALS is immune cell presence in areas of the spine with nerve cell degeneration.

However, it’s not clear why the inflammation occurs and if it is the first step of damage or if some type of disease process happens before the inflammation in ALS.  

Genetics 

About 10% of the time, ALS is familial. In these cases, it may be inherited in an autosomal dominant pattern, which means that a person who inherits a mutated gene from one parent will develop the disease. 

The most common inherited mutations (genetic changes) of ALS affect the SOD1, TDP-43, FUS, and C9orf72 genes, and several other genes have also been identified.

The exact roles of these genes and how they could lead to ALS are not completely clear, but research about what these genes could do in the process of causing ALS is ongoing.

Lifestyle Risk Factors 

A few environmental and lifestyle factors have been linked to ALS. The links are not strong, and it is not clear exactly how they might affect the disease.

Lifestyle risk factors for ALS: 

• Exposure to diesel exhaust, lead, silica, organic dust, extremely low-frequency magnetic fields, and electric shocks
• Intense physical activity in your occupation 
• Certain occupations, including construction, farming, fishing, logging, and hunting
• Long-term exposure to air pollution
• Red and processed meat, animal protein, sodium, zinc, and glutamic acid

A slightly reduced risk for ALS has been associated with consuming coffee, tea, whole-grain bread, raw vegetables, and citrus fruits.

With all of these lifestyle factors, researchers have not found whether ALS could be caused by these exposures or whether it is only an association. 

Summary 

ALS is caused by the degeneration of motor neurons in the lateral and anterior horns of the spinal cord. Inflammation may have a role in this neurodegeneration.

Several risk factors have been described in association with ALS. They include older age, being male, and exposure to air pollution and certain environmental toxins. However, these risk factors are very common in the general population. Therefore, they do not provide enough predictive value to warrant early surveillance or treatment for ALS.

Some genetic patterns have been linked with ALS, including a familial pattern of inheritance and genetic mutations. This accounts for approximately 10% of ALS, and the remaining 90% are considered idiopathic—without a known cause.

A Word From Verywell

If you have been diagnosed with ALS, it’s important for you to know that nothing you did caused you to develop this condition. Although there is a slight genetic link and an association with environmental exposure, researchers have not discovered a cause that explains why some people develop this disease and others do not.

If you are diagnosed with ALS, it's worth considering whether you may have a familial form of ALS. This way, others in your family could get tested and treated at an early stage or make reproductive choices if they choose to do so.