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als what causes it

ALS (amyotrophic lateral sclerosis) is caused by a mix of genetic susceptibility and environmental/biological factors, but in most people doctors still cannot point to one single clear cause.

Quick Scoop: What Causes ALS?

1. Two main types: sporadic vs familial

  • Sporadic ALS (about 90–95% of cases):
    • No clear single cause identified, so it’s called “idiopathic.”
* Thought to result from a combination of underlying genetic risk plus lifetime environmental exposures.
  • Familial ALS (about 5–10% of cases):
    • Clearly runs in families and is linked to inherited gene mutations.
* Often passed in an autosomal dominant way (you may only need one copy of the faulty gene from one parent).

2. Key genes involved

Researchers have found several genes that, when mutated, can directly cause familial ALS and also explain a portion of sporadic cases.

Some of the most important:

  • C9orf72:
    • The most common known genetic cause of ALS worldwide.
* Involves abnormal repeat expansions in the gene, and is also strongly linked to frontotemporal dementia (FTD).
  • SOD1:
    • One of the earliest discovered ALS genes; mutations can make this antioxidant enzyme misfold and become toxic.
* Accounts for a significant fraction of familial ALS cases (roughly 15% in some European groups, higher in some Asian populations).
  • Other genes (like TARDBP, FUS and others) are also implicated and together explain most, but not all, familial ALS cases and a minority of sporadic cases.

3. What’s happening in the nerve cells?

ALS mainly affects motor neurons (nerve cells that control voluntary muscles), and several biological processes seem to go wrong at once:

  • Abnormal proteins and aggregation:
    • A protein called TDP-43 is misfolded and abnormally accumulates in more than 95% of sporadic ALS cases, disrupting how cells handle RNA and making neurons vulnerable.
  • Oxidative stress:
    • An imbalance between damaging reactive oxygen species and the body’s antioxidant defenses can injure motor neurons.
  • Mitochondrial dysfunction:
    • The “powerhouses” of the cell (mitochondria) do not produce energy properly, which stresses and damages neurons.
  • Glutamate excitotoxicity:
    • Too much of the neurotransmitter glutamate overstimulates neurons and contributes to their death; one ALS drug, riluzole, works partly by reducing glutamate activity.
  • Immune/inflammation changes:
    • Overactive or poorly regulated immune cells in the brain and spinal cord (like microglia) may worsen neuronal damage.

Think of it as several “hits” to the motor neurons over time—genetic vulnerability plus cellular stressors—eventually crossing a threshold where cells start to degenerate.

4. Environmental and lifestyle risk factors

No single environmental trigger has been proven to cause ALS by itself, but several factors are associated with a higher risk:

  • Smoking:
    • Consistently linked to increased ALS risk; in some studies, women who smoke after menopause seem at particularly high risk.
  • Possible toxin exposures:
    • Lead and certain other metals, pesticides, solvents, and other industrial chemicals have been associated with higher risk in some studies, though no single agent is definitively “the” cause.
  • Military service / intense physical or environmental stress:
    • Several studies suggest people who served in the military may have a higher risk, possibly due to combined physical exertion, chemicals, trauma, or other exposures, but the exact reasons remain unclear.
  • Head or electrical injuries and other physical trauma:
    • Some research has linked traumatic injuries (including head injury) and electric shock with ALS, but evidence is mixed and not fully conclusive.

Overall, the current thinking is a “multi-step” model: you may be born with certain gene variants, and over decades your cells experience multiple stresses (toxins, inflammation, oxidative stress, etc.) until enough damage accumulates and ALS appears.

5. What this means for individuals

  • For most people with ALS, there is no obvious thing they did “wrong” and no single exposure that clearly explains the disease.
  • If multiple close family members have ALS or related conditions like frontotemporal dementia, genetic counseling and possible genetic testing can be considered.
  • Research is very active, especially around genetics, protein aggregation (like TDP-43 and SOD1), immune changes, and environmental risks, because understanding causes is key to developing better treatments.

Information gathered from public forums or data available on the internet and portrayed here.