TARDBP and motor neuron disorder: TDP-43 (TAR DNA-bindingprotein 43) is a key pathological hallmark associated with ALS andrelated motor neuron diseases.211 Lossof TDP-43 from the nucleus and abnormal accumulation of TDP-43 aggregatesin the cytoplasm of affected neurons is a prominent pathological featureobserved in the majority (>97%) of cases, particularly in sALS.212−215 TDP-43 pathology correlates with disease severity and progression,suggesting a central role in ALS pathogenesis.216