ALSの病理

Neuropathology of Amyotrophic Lateral Sclerosis

筋萎縮性側索硬化症（ALS）は病理学的に上位運動ニューロン（UMN）と下位運動ニューロン（LMN）がさまざまな程度の組合せで障害される疾患である。孤発性ALSのLMNではTDP-43の核内局在が消失し，細胞質に異常に凝集して封入体を形成する。TDP-43の封入体は運動ニューロン系を超えて神経細胞とグリア細胞に分布する。病変の進展機序に，TDP-43のプリオン病様蛋白伝播仮説が提唱されている。

Abstract

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.