TARDBP and amyotrophic lateral sclerosis: In contrast, these regions are either spared or affected later in the course of ALS, where pathology spreads from motor neurons [65] While no significant differences in relative PRS by TDP-43 burden were observed in either ALS characteristic region evaluated, it is possible that this is confounded by neuron loss, particularly for the spinal cord where neuronal dropout can lower TDP-43 burden.