Amyotrophic lateral sclerosis (ALS) often starts at middle age, but I didn't find any suggestion why. Something seems to trigger the symptoms in middle age.

If I am not mistaken, the sporadic ALS is not genetic, but there are genetic variants. So these genes are with the person all his life. But why do the disease symptoms often start only in middle age?


Short answer
The causes of ALS are not well known. Some familial types are associated with toxic proteins, susceptibility to toxins and defective protein metabolism. My personal 2-cents is that metabolic and toxicologic defects tend to cause cumulative tissue damage over time, perhaps explaining the delayed onset.

Amyotrophic lateral sclerosis (ALS), is a progressive, fatal disease characterized by the gradual degeneration and death of motor neurons.

In 90 to 95 percent of all ALS cases, the disease is sporadic, meaning that it appears apparently at random. Individuals have no family history of ALS, and their family members are not considered to be at increased risk for developing it.

About 5 to 10 percent of all ALS cases are inherited. About one-third of all familial cases result from a defect in a gene known as “chromosome 9 open reading frame 72,” or C9orf72. The function of this gene is still unknown. Another 20 percent of familial cases result from mutations in the gene that encodes the enzyme copper-zinc superoxide dismutase 1 (SOD1). In case of mutations in the SOD1 gene it is though that mutant SOD1 protein is toxic.

Other inherited forms are believed to change in the processing of RNA, that may lead to ALS-related motor neuron degeneration. Other gene mutations implicate defects in protein recycling. And still others point to possible defects in the structure and shape of motor neurons, as well as increased susceptibility to environmental toxins.

Source: NIH - ALS Facts Sheet

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  • $\begingroup$ Thank you, Alice. Also for editing my question. I read this source before. If we talk about familial ALS - it's looks more clear. Accumulation of toxic mutant protein, for example. Some sort of accumulating defects. But what about sporadic? ~90% of the ALS. And also - sometimes ALS starts in young people. $\endgroup$ – Robertos Oct 15 '15 at 12:48
  • $\begingroup$ @VGranin - no worries, happy to help. The disease etiology of the sporadic cases are, as far as I understand and as stated in my answer, often unknown. Because they, seemingly, don't have a genetic background, it is probably very hard to pinpoint what is at fault in these folks. In other words - I don't know and as far as I can see, no one really does. That is, implicitly, what 'sporadic' means - random occurrence / cause unknown. $\endgroup$ – AliceD Oct 15 '15 at 12:51
  • $\begingroup$ Yeh I know that I will not get some proved reason. But maybe there is some studies that have some good suggestions based on some evidence ... Also about the genetics - I think that in all cases there must be some genetic background. The environment could trigger it - but must be something wrong in the genes from the beginning. And in middle ages the body gets weaker - so thinks go wrong more easily. It's only my suggestion. $\endgroup$ – Robertos Oct 15 '15 at 13:06

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