title: Relationship in the formation process between neurofibrillary tangles and Lewy bodies in the hippocampus of dementia with Lewy bodies brains.
abstract: Using tau immunohistochemistry and alpha-synuclein immunohistochemistry, we quantitatively investigated the most frequent sites and the formation process of neurofibrillary tangles (NFT) and Lewy bodies (LB) in the hippocampus from 20 patients with dementia with Lewy bodies (DLB). NFT were most frequently found in the CA2 and the subiculum-pre-CA1, while LB were most frequently found in the CA3-4 and the subiculum-pre-CA1. In the intrahippocampal routes of the perforant pathway, tau immunoelectron microscopy demonstrated distal axons containing aggregated tau-positive microtubules, while alpha-synuclein immunoelectron microscopy revealed terminal axons containing aggregated alpha-synuclein-positive tubular or filamentous components. These findings suggest that NFT and LB are first formed in the CA2 and the CA3-4 related to degeneration of the nonperforating route of the perforant pathway, respectively, and subsequently in the subiculum-pre-CA1 chiefly related to degeneration of the perforating route. Coexistence of NFT and LB in the same neurons was found most frequently in the subiculum-pre-CA1. In addition, coexistence of tau and alpha-synuclein was found in terminal axons of the perforant pathway, and tau accumulated not in paired helical filaments but in the periphery of alpha-synuclein-positive components immunoelectron-microscopically, suggesting that alpha-synuclein stimulates the accumulation of phosphorylated tau in terminal axons.
authors.affiliation: Department of Psychiatry, Yokohama City University School of Medicine, 3-9 Fukuura, Yokohama 236-0004, Kanazawa, Japan. iseki@med.yokohama-cu.ac.jp
authors.forename: Eizo
authors.initials: E
authors.lastname: Iseki
authors.forename: Noriko
authors.initials: N
authors.lastname: Takayama
authors.forename: Wami
authors.initials: W
authors.lastname: Marui
authors.forename: Kenji
authors.initials: K
authors.lastname: Uéda
authors.forename: Kenji
authors.initials: K
authors.lastname: Kosaka
mesh_terms: D000368:Aged; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D016631:Lewy Bodies / Q000378:metabolism / Q000473:pathology*; D020961:Lewy Body Disease / Q000378:metabolism / Q000473:pathology*; D016253:Microscopy, Immunoelectron; D009419:Nerve Tissue Proteins / Q000378:metabolism; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology*; D019580:Perforant Pathway / Q000378:metabolism / Q000473:pathology; D051843:Synucleins; D051844:alpha-Synuclein; D016875:tau Proteins / Q000378:metabolism
chemical_list: D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein; D016875:tau Proteins