title: Hippocampal sclerosis in the parkinsonism-dementia complex of Guam: quantitative examination of neurons, neurofibrillary tangles, and TDP-43 immunoreactivity in CA1.
abstract: The cornu ammonis 1 (CA1) area in the hippocampus of the parkinsonism-dementia complex (PDC) of Guam was examined quantitatively with special references to the number of neurons, intraneuronal (i) and extracellular (e) neurofibirillary tangles (NFTs), and TDP-43 (43-kDa trans-activation-responsive region DNA-binding protein)-immunopositive structures, in 24 Chamorro patients with PDC of Guam and seven control Chamorro Guamanians (both groups having no ischemic or anoxic complications). The results were that: (i) in the patients with mildly involved PDC, total numbers of neurons, iNFTs and eNFTs were almost the same as those of neurons of controls; (ii) in patients severely involved, total numbers of neurons, iNFTs and eNFTs decreased markedly; (iii) the decrease of the number of pyramidal neurons in CA1 with positive nuclear TDP-43 was intimately correlated with the decrease in total neuron numbers; (iv) whereas the numbers of neurons and TDP-43-immunopositive intracytoplasmic aggregation in the CA1 area were inversely correlated; and (v) depression of nuclear TDP-43 immuonostainability was not affected by the presence or absence of NFTs. In conclusion, hippocampal sclerosis exists in PDC; there is a possibility of elimination of eNFTs which appeared in the CA1 in patients with PDC and loss of the neurons correlates with disappearance of nuclear TDP-43, but not with appearance of intraneurocytoplasmic TDP-43 aggregation or iNFTs.
authors.affiliation: Department of Brain Disease Research, Shinshu University School of Medicine, Matsumoto, Nagano, Japan.
authors.forename: Kiyomitsu
authors.initials: K
authors.lastname: Oyanagi
authors.affiliation: Department of Neurology, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Chiba, Japan.
authors.forename: Mineo
authors.initials: M
authors.lastname: Yamazaki
authors.affiliation: Department of Brain Disease Research, Shinshu University School of Medicine, Matsumoto, Nagano, Japan.|Department of Neurology, University of Occupational and Environmental Health, Kitakyushu, Fukuoka, Japan.
authors.forename: Tomoyo
authors.initials: T
authors.lastname: Hashimoto
authors.affiliation: Department of Brain Disease Research, Shinshu University School of Medicine, Matsumoto, Nagano, Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Asakawa
authors.affiliation: Department of Neuropathology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Wakabayashi
authors.affiliation: Department of Pathology, Brain Research Institute, Niigata University, Niigata, Niigata, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Takahashi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004268:DNA-Binding Proteins / Q000378:metabolism; D003704:Dementia / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D005110:Extracellular Space; D005260:Female; D006141:Guam; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D020734:Parkinsonian Disorders / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D012598:Sclerosis
chemical_list: D004268:DNA-Binding Proteins; C000598624:TARDBP protein, human
keywords: CA1; Parkinsonism-dementia complex; TDP-43; hippocampal sclerosis; neurofibrillary tangle