Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative diseases characterized by selective and progressive loss of neurons in the central nervous system, bring heavy burden to society and family. More and more evidences have shown that ALS and FTD overlap in clinical manifestations, pathological changes and genetic characters. Compared with ALS or FTD, ALS-FTD has faster disease progression and shorter survival time. At present, the etiology and pathogenesis of ALS and FTD are unclear. Many studies have revealed that there is a common pathological basis for ALS and FTD:
TDP-43 (transactivation response DNA-binding protein 43 kDa)-positive inclusion bodies exist in the remnant neurons and glial cells of the nervous system. Studies have shown that TDP-43 protein in the central nervous system of patients with ALS-FTD loses normal nuclear localization and aggregates in the cytoplasm to form inclusion bodies. It is speculated that the loss of normal function and acquired neurotoxicity of TDP-43 may be one of the initiating factors of ALS-FTD. This paper reviews the latest research progress in the pathogenesis of ALS-FTD.