Figure 1. Clinicopathological Classification of TDP-43 Proteinopathies.

TDP-43 proteinopathies are defined based upon which brain regions contain the greatest abundance of pathology. (A) in ALS, abnormal TDP-43 inclusions are found in both the upper motor neurons of the primary motor cortex (green) as well as lower motor neurons, including those of the anterior horn of the spinal cord (purple). This pattern of pathology correlates with the clinical symptoms of motor neuron dysfunction. (B) FTLD is characterized by abnormal TDP-43 inclusions predominantly affecting cells in the frontal (pink) and temporal (orange) lobes, correlating with the behavioral disturbances classically seen in FTLD. (C) LATE has only recently been described and consensus criteria propose four stages of disease defined by the brain regions involved by abnormal inclusions of TDP-43. While a stage 0 indicates no abnormal TDP-43 aggregates, in stage one the aggregates are limited to the amygdala (yellow); the clinical implications of stage 1 LATE are not well understood. In stage 2 both amygdala and hippocampus (orange) are involved, while by stage 3, neocortex (pink) is also involved. These later stages correlate well with clinical symptoms, including amnestic complaints (hippocampus) and more global cognitive dysfunction (neocortex).