TARDBP and amyotrophic lateral sclerosis: A postmortem study hypothesized that abnormal but soluble TDP-43 in the Betz cells, where TDP-43 pathology is considered to be initiated, could be an early mechanism of ALS; the hypothesis arose from the fact that aggregation of p-TDP-43 was relatively sparse in the Betz cells compared with mislocalization of nuclear TDP-43 [87].