Developmental stages of cortical Lewy bodies and their relation to axonal transport blockage in brains of patients with dementia with Lewy bodies.
We investigated 10 dementia with Lewy bodies (DLB) brains showing various degrees of Lewy pathology using alpha-synuclein-immunohistochemistry, and morphologically divided cortical Lewy bodies (LB) into six developmental stages. Further, we demonstrated the ultrastructure of each stage of cortical LB using alpha-synuclein-immunoelectron microscopy. In the initial stage, alpha-synuclein accumulated in part of the neuronal cytoplasm without filamentous components, then formed LB and LB-related neurites composed of granulo-filamentous components. Finally, LB degraded to extracellular LB composed of loose filamentous components with involved astroglial processes. In addition, we immunohistochemically investigated the accumulation of axonal transported substances in cortical LB, and showed that APP, chromogranin-A, synphilin-1 and synaptophysin accumulated in cortical LB from stages 1, 2, 3 and 4, respectively. These findings suggest that chronic axonal transport blockage is implicated in the development of cortical LB in DLB brains.
Katsuse
Omi
O
Department of Psychiatry, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
Iseki
Eizo
E
Marui
Wami
W
Kosaka
Kenji
K
D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D001370:Axonal Transport / Q000502:physiology*; D002352:Carrier Proteins / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology*; D053379:Chromogranin A; D002864:Chromogranins / Q000378:metabolism; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D016631:Lewy Bodies / Q000378:metabolism / Q000473:pathology*; D020961:Lewy Body Disease / Q000378:metabolism / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D016900:Neurofilament Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000378:metabolism; D016708:Synaptophysin / Q000378:metabolism; D051843:Synucleins; D014404:Tubulin / Q000378:metabolism; D014452:Ubiquitins / Q000378:metabolism; D051844:alpha-Synuclein
D016564:Amyloid beta-Protein Precursor; D002352:Carrier Proteins; D053379:Chromogranin A; D002864:Chromogranins; D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins; D010446:Peptide Fragments; C497604:SNCA protein, human; C118958:SNCAIP protein, human; D016708:Synaptophysin; D051843:Synucleins; D014404:Tubulin; D014452:Ubiquitins; D051844:alpha-Synuclein