Localization of MAP1-LC3 in Vulnerable Neurons and Lewy Bodies in Brains of Patients With Dementia With Lewy Bodies

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 (DL...

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Published in:Journal of neuropathology and experimental neurology 2011-04, Vol.70 (4), p.264-280
Main Authors: Higashi, Shinji, Moore, Darren J, Minegishi, Michiko, Kasanuki, Koji, Fujishiro, Hiroshige, Kabuta, Tomohiro, Togo, Takashi, Katsuse, Omi, Uchikado, Hirotake, Furukawa, Yoshiko, Hino, Hiroaki, Kosaka, Kenji, Sato, Kiyoshi, Arai, Heii, Wada, Keiji, Iseki, Eizo
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Alzheimer Disease - pathology
Amyloid beta-Peptides - metabolism
Autophagy
Biological and medical sciences
Blotting, Western
Brain - pathology
Cell Count
Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases
Entorhinal Cortex - pathology
Female
Fluorescent Antibody Technique
HEK293 Cells
Humans
Immunohistochemistry
Lewy Bodies - metabolism
Lewy Bodies - pathology
Lewy Body Disease - pathology
Lysosomal Membrane Proteins - genetics
Lysosomal Membrane Proteins - physiology
Lysosomal-Associated Membrane Protein 2
Male
Medical sciences
Microtubule-Associated Proteins - metabolism
Middle Aged
Neurofibrillary Tangles - pathology
Neurology
Neurons - metabolism
Neurons - pathology
Plasmids - genetics
rab GTP-Binding Proteins - genetics
rab GTP-Binding Proteins - physiology
rab7 GTP-Binding Proteins
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Summary: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.
ISSN:0022-3069
1554-6578
DOI:10.1097/NEN.0b013e318211c86a