Neuropathology of Amyotrophic Lateral Sclerosis

The basic neuropathology of amyotrophic lateral sclerosis (ALS) is defined as the involvement of the upper motor neurons system (UMN) and the lower motor neuron system (LMN), with variable degree and combination. The characteristic pathological feature of sporadic ALS is cytoplasmic mislocalization of nuclear TDP-43 and aggregation of abnormally phosphorylated TDP-43 inclusions in cytoplasm in LMN, UMN and glial cells. TDP-43 inclusions correlate with cell loss and distribute beyond the UMN and LMN system. It has been proposed that phosphorylated TDP-43 (pTDP-43) disseminates in a sequential pattern along the motor pathways, as suggested by the hypothesis of corticofugal ('prion-like') propagation of misfolded proteins in ALS.