On the possibility of autolysosomal processing of skein-like inclusions. Electron microscopic observation in a case of amyotrophic lateral sclerosis.

Abstract

Hyaline-like inclusions (HLIs) and skein-like inclusions (SLIs) were recently observed in the lower motor neurons in amyotrophic lateral sclerosis (ALS). HLIs mainly consist of randomly arranged neurofilaments and abnormally large (about 15 nm) fibrils, while SLIs comprise bundles of the abnormally large fibrils alone. Although the abnormal fibrils have been reported to be ubiquitinated in both types of inclusions, their final catabolic destination in the neurons is unknown. Electron microscopic observation of the lower motor neurons in an ALS case revealed several neurons containing SLIs in addition to ones containing HLIs. Bundles of SLIs, which were located close to HLIs or were observed by themselves without an HLI, were frequently associated with flattened cisterns; some were wrapped, some were completely sequestrated, and some were demarcated together with a portion of moderately electron dense cytoplasm by cisterns or double-membraned units. These features resemble reported early stages in the formation of autolysosomes, and thus indicate that at least some of the bundles of SLIs or parts of them in the lower motor neurons in ALS undergo degradation through the autolysosomal pathway.