Existing clinical trials are mostly aimed at patients with mild to moderate AD, and TDP-43 pathology is mostly seen in the oldest-old and those with a more severe clinical phenotype (Wilson et al., 2011; Robinson et al., 2014; Nelson et al., 2019); between 20% and 50% of AD cases, and 75% of severe cases exhibit pathophysiological TDP-43 (Amador-Ortiz et al., 2007; Uryu et al., 2008). The gene discussed is TARDBP; the disease is Alzheimer disease.