What is the core pathological finding in ALS?
The core pathological finding in ALS is motor neuron death in the motor cortex and spinal cord. Degeneration of the corticospinal axons causes thinning and scarring (sclerosis) of the lateral aspects of the spinal cord. In addition, as the brain stem and spinal motor neurons die, there is thinning of the ventral roots and denervational atrophy (amyotrophy) of the muscles of the tongue, oropharynx, and limbs.
Are there many genetic variants of ALS?
Evolving technologies for gene mapping and DNA analysis have facilitated the identification of multiple ALS genes. SOD1 (encoding superoxide dismutase 1) was the first ALS gene to be identified, in 1993. At least 25 genes have now been reproducibly implicated in familial ALS, sporadic ALS, or both. Correlations between genetic variants and different clinical profiles in ALS, such as age at onset, disease duration, and site of onset, have been defined.