title: Localization of MAP1-LC3 in vulnerable neurons and Lewy bodies in brains of patients with dementia with Lewy bodies.
abstract: There is emerging evidence implicating a role for the autophagy-lysosome pathway in the pathogenesis of Lewy body disease. We investigated potential neuropathologic and biochemical alterations of autophagy-lysosome pathway-related proteins in the brains of patients with dementia with Lewy bodies (DLB), Alzheimer disease (AD), and control subjects using antibodies against Ras-related protein Rab-7B (Rab7B), lysosomal-associated membrane protein 2 (LAMP2), and microtubule-associated protein 1A/1B light chain 3 (LC3). In DLB, but not in control brains, there were large Rab7B-immunoreactive endosomal granules. LC3 immunoreactivity was increased in vulnerable areas of DLB brains relative to that in control brains; computerized cell counting analysis revealed that LC3 levels were greater in the entorhinal cortex and amygdala of DLB brains than in controls. Rab7B levels were increased, and LAMP2 levels were decreased in the entorhinal cortex of DLB brains. In contrast, only a decrease in LAMP2 levels versus controls was found in AD brains. LC3 widely colocalized with several types of Lewy pathology; LAMP2 localized to the periphery or outside of brainstem-type Lewy bodies; Rab7B did not colocalize with Lewy pathology. Immunoblot analysis demonstrated specific accumulation of the autophagosomal LC3-II isoform in detergent-insoluble fractions from DLB brains. These results support apotential role for the autophagy-lysosome pathway in the pathogenesis of DLB.
authors.affiliation: PET/CT Dementia Research Center, Juntendo Tokyo Koto Geriatric Medical Center, Juntendo University School of Medicine, Shinsuna, Koto-ku, Tokyo, Japan. higashi-sj@igakuken.or.jp
authors.forename: Shinji
authors.initials: S
authors.lastname: Higashi
authors.forename: Darren J
authors.initials: DJ
authors.lastname: Moore
authors.forename: Michiko
authors.initials: M
authors.lastname: Minegishi
authors.forename: Koji
authors.initials: K
authors.lastname: Kasanuki
authors.forename: Hiroshige
authors.initials: H
authors.lastname: Fujishiro
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kabuta
authors.forename: Takashi
authors.initials: T
authors.lastname: Togo
authors.forename: Omi
authors.initials: O
authors.lastname: Katsuse
authors.forename: Hirotake
authors.initials: H
authors.lastname: Uchikado
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Furukawa
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Hino
authors.forename: Kenji
authors.initials: K
authors.lastname: Kosaka
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Sato
authors.forename: Heii
authors.initials: H
authors.lastname: Arai
authors.forename: Keiji
authors.initials: K
authors.lastname: Wada
authors.forename: Eizo
authors.initials: E
authors.lastname: Iseki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001343:Autophagy; D015153:Blotting, Western; D001921:Brain / Q000473:pathology*; D002452:Cell Count; D018728:Entorhinal Cortex / Q000473:pathology; D005260:Female; D005455:Fluorescent Antibody Technique; D057809:HEK293 Cells; D006801:Humans; D007150:Immunohistochemistry; D016631:Lewy Bodies / Q000378:metabolism* / Q000473:pathology*; D020961:Lewy Body Disease / Q000473:pathology*; D052119:Lysosomal-Associated Membrane Protein 2; D051907:Lysosomal Membrane Proteins / Q000235:genetics / Q000502:physiology; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology*; D010957:Plasmids / Q000235:genetics; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000502:physiology; D000090802:rab7 GTP-Binding Proteins
chemical_list: D016229:Amyloid beta-Peptides; C497811:LAMP2 protein, human; D052119:Lysosomal-Associated Membrane Protein 2; D051907:Lysosomal Membrane Proteins; C477012:MAP1LC3A protein, human; C502070:MAP1LC3B protein, human; D008869:Microtubule-Associated Proteins; D000090802:rab7 GTP-Binding Proteins; D020691:rab GTP-Binding Proteins