title: Localization of CHMP2B-immunoreactivity in the brainstem of Lewy body disease.
abstract: Alpha-synuclein (αS) is one of the major constituents of Lewy bodies (LBs). Several lines of evidence suggest that the autophagy-lysosome pathway (ALP) is involved in the removal of αS. We have previously reported that granulovacuolar degeneration (GVD) in neurons involved a subunit of the endosomal sorting complexes required for transport (ESCRT). In this study, we examined the association between alpha-synucleinopathy and autophagy through immunohistochemical analysis of charged multivesicular body protein 2B (CHMP2B), a component of the ESCRT-pathway. We examined the brainstems of 17 patients with Parkinson's disease (PD), incidental Lewy body disease (ILBD), multiple system atrophy (MSA), and Alzheimer's disease (AD) immunohistochemically using antibodies against phosphorylated αS (pαS), phosphorylated tau and CHMP2B. LBs and a proportion of glial cytoplasmic inclusions (GCIs) were immunopositive for pαS and CHMP2B. Neurons containing CHMP2B-immunoreactive granules were detected in PD and ILBD, but not in MSA and AD brains. CHMP2B immunoreactivity was increased in the dorsal motor nucleus of the vagus nerve (DMNX) in PD and ILBD brains, relative to that in MSA and AD. These findings indicate that the ESCRT-pathway is implicated in the formation of αS inclusions, especially in PD and ILBD.
authors.affiliation: Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan. takashi-kurashige@hiroshima-u.ac.jp
authors.forename: Takashi
authors.initials: T
authors.lastname: Kurashige
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Takahashi
authors.forename: Yuu
authors.initials: Y
authors.lastname: Yamazaki
authors.forename: Masanori
authors.initials: M
authors.lastname: Hiji
authors.forename: Yuishin
authors.initials: Y
authors.lastname: Izumi
authors.forename: Takemori
authors.initials: T
authors.lastname: Yamawaki
authors.forename: Masayasu
authors.initials: M
authors.lastname: Matsumoto
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology; D001344:Autopsy; D001933:Brain Stem / Q000473:pathology*; D056827:Endosomal Sorting Complexes Required for Transport / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D002479:Inclusion Bodies / Q000473:pathology; D016631:Lewy Bodies / Q000473:pathology; D020961:Lewy Body Disease / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D019578:Multiple System Atrophy / Q000473:pathology; D010300:Parkinson Disease / Q000473:pathology
chemical_list: C503812:CHMP2B protein, human; D056827:Endosomal Sorting Complexes Required for Transport