Background: Amyotrophic lateral sclerosis (ALS) is an intractable neurodegenerative disease of the central nervous system. Despite an unknown etiology, its pathophysiology is considered to be heterogeneous. Recent reports have highlighted the presence of disease-associated microglia (DAM) in the lesions of various neurodegenerative diseases, including that in ALS model animals. However, limited information is available regarding DAM in sporadic cases of ALS in humans.Methods: This study analyzed data from 30 patients with ALS. Autopsy samples of cervical and lumbar lesions obtained from each patient were stained with anti-TMEM119, anti-Iba1, anti-CX3CR1, anti-CD68, and anti-thrombomodulin antibodies to investigate the role of microglia in ALS pathogenesis. Additionally, we explored the relationship between microglia surface markers and clinical data, which included lower motor neuron loss, clinical symptoms, and disease duration.Results: Pathological examination revealed at least two subgroups of spinal cord lesions in ALS i.e., the TMEM119+ microglia-positive group and TMEM119+ microglia-negative group. The TMEM119+ group exhibited the expression of the microglial activation marker CD68 and endothelial activation marker thrombomodulin, indicating the presence of inflammatory processes in ALS lesions. No clinical differences were observed between the TMEM119+ microglia-positive and TMEM119+ microglia-negative groups, except for differences in complications related to urinary tract infection.Discussion: Since DAM suppresses TMEM119 expression, the TMEM119+ microglia-positive group may indicate DAM-independent inflammatory neurodegeneration.