This is a progressive, fatal neurodegenerative disorder, more specifically, the most common form of MND (motor neurone disorder), since 80-90% of MND patients are affected by ALS. The disease typically begins to manifest in people between 50 and 70 years old and is slightly more common in men. Some of the most common symptoms consist mainly of motor symptoms, however in many patients there have been found cognitive or behavioural changes aswell, but it is a spectrum disorder with FTD (frontotemporal dementia) being the most severe form.

Aetiology:

It is considered a sporadic disease (which means that it appears irregularly and in an unpredictable way) and even if it is considered familial (which means that it’s present in members of the same family but it doesn’t actually follow the Mendelian laws, they just have a shared genetic component among family members) studies suggest that heritability may account for up to 50%.

Pathophysiology:

ALS provokes a degeneration of both the upper motor neurones (UMN) and the lower motor neurones (LMN).
The first one can cause spasticity, brisk reflexes, and pathological UMN signs (for example: Hoffmann’s sign, Babinski response , jaw jerk, and more).
On the other hand, the LMN degeneration leads to anterior horn cell loss in the spinal cord, resulting in muscle wasting, fasciculations, and flaccid weakness.
While ALS can be attributed to many factors, some of the most important ones are protein misfolding and aggregation; in fact, the abnormal accumulation of TDP-43 and SOD1 proteins has been observed in affected neurons.
Another important factor is altered RNA signalling, which, when combined with oxidative stress and mitochondrial malfunction, causes problems in the cell's energy metabolism. This leads, among other things, to neuroinflammation that may be beneficial initially but becomes harmful over time. The end result is that axonal transport, cellular communication, and the regenerative abilities of the cell get progressively worse.
These mechanisms combined result in progressive motor neurone degeneration and the combination of UMN and LMN features.
Risk Factors:
ALS is probably a result of both genetic susceptibility and the environment in which one was raised and lived.
Over 40 ALS-associated genes have been identified; in particular, genes such as C9orf72 and SOD1 are more likely to cause the disease, but they aren’t the only factors.
As a matter of fact the risk of contracting the disease increases with age with its peak from 50 to 70 years and males are slightly more likely to fall sick (with a ratio of 1.5:1). Environmental triggers such as military service, exposure to: pesticides, solvents, heavy metals, and cyanotoxins; smoking and possibly elite athleticism (the researches are still going) play a big part in the increase of risk.