Cognitive dysfunction in patients with amyotrophic lateral sclerosis is associated with spherical or crescent-shaped ubiquitinated intraneuronal inclusions in the parahippocampal gyrus and amygdala, but not in the neostriatum

Skeins or skein-like inclusions, one of the two types of ubiquitinated intr aneuronal inclusions in amyotrophic lateral sclerosis (ALS), in the neostri atum are not specific to the disease, but it has not yet been determined wh ether the other, spherical or crescent-shaped inclusions (SCI) are pathogno monic. To clarify this and also to investigate whether the distribution of SCI in particular brain regions is associated with clinical parameters, we examined the occurrence of SCI in the brains of 24 patients with ALS and 94 controls. SCI in the neostriatum were specifically detected in 54% of the ALS cases, but not in any of the controls. No apparent phenotypic denominat or, such as disease duration or the occurrence of dementia, correlated to t he distribution of SCI in the neostriatum in ALS cases. On the other hand, the occurrence of SCI in both the second and third layers of the parahippoc ampal gyrus and amygdala was significantly correlated to the presence of de mentia in ALS cases. SCI were distributed in association with each other am ong the parahippocampal gyrus, dentate gyrus of the hippocampus and amygdal a, but not between the spinal anterior hom and any non-motor-associated bra in regions. These findings suggest that these particular brain regions migh t be significantly involved in the neurodegenerative process associated wit h ALS. The relationship of SCI to either ALS pathogenesis or cognitive dysf unction depends on the brain regions in which they are distributed, and thi s indicates that the neurodegenerative processes in ALS proceed differentia lly in particular motor-associated and nonmotor-associated brain regions.