New ubiquitin-positive intraneuronal inclusions in the extra-motor cortices in patients with amyotrophic lateral sclerosis.

We examined the brains of 27 amyotrophic lateral sclerosis (ALS) patients and 50 controls by light, electron and immunoelectron microscopy. Ubiquitin-positive intraneuronal inclusions were seen in the hippocampal granular cell layer and entorhinal cortex of 7 out of the ALS patients. Similar inclusions could not be seen in the same areas in the controls. They were not seen on light microscope staining, nor did they show anilinophilia, argentophilia or congophilia. They were not reacted with other antibodies including neurofilament, tau and paired helical filament (PHF). Immunoelectron microscopy by the preembedding method using anti-ubiquitin antibody showed those inclusions consist of loosely arranged lineal filaments and granular materials. These results suggest that ubiquitin-related cytoskeletal abnormalities are present in cerebral non-motor small neurons in some sporadic ALS patients.