title: Amyloid cored plaques in Tg2576 transgenic mice are characterized by giant plaques, slightly activated microglia, and the lack of paired helical filament-typed, dystrophic neurites.
abstract: We examined the brains of Tg2576 transgenic mice carrying human amyloid precursor protein with the Swedish mutation and Alzheimer's disease (AD) by means of immunohistochemistry and electron microscopy to clarify the characteristics of amyloid-associated pathology in the transgenic mice. In 12- to 29-month-old Tg2576 mice, congophilic cored plaques in the neocortex and hippocampus were labeled by all of the Abeta1-, Abeta40- and 42-specific antibodies, as seen in the classical plaques in AD. However, large-sized (>50 micro m in core diameter) plaques were seen more frequently in the older mice (18-29 months) than in those with AD (approximately 20% vs 2% in total cored plaques), and Tg2576 mice contained giant plaques (>75 micro m in core diameter), which were almost never seen in the brain of those with AD. Neither thread-like structures nor peripheral coronas were observed in the cored plaques of the transgenic mice in the silver impregnations. Immunohistochemically, plaque-accompanied microglia showed a slight enlargement of the cytoplasm with consistent labeling of Mac-1 and macrosialin (murine CD68), and with partial labeling of Ia antigen and macrophage-colony stimulating factor receptor. Ultrastructurally, the microglia surrounding the extracellular amyloid fibrils in the large, cored plaques showed some organella with phagocytic activity, such as secondary lysosomal, dense bodies, but intracellular amyloid fibrils were not evident. Dystrophic neurites in the plaques of the transgenic mice contained many dense multilaminar bodies, but no paired helical filaments. Our results suggest that giant cored plaques without coronas or paired helical filament-typed, dystrophic neurites are characteristic in Tg2576 mice, and that plaque-associated microglia in transgenic mice are activated to be in phagocytic function but not sufficient enough to digest extracellularly deposited amyloid fibrils.
authors.affiliation: Department of Pathology, Gunma University School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan. achie@med.gunma-u.ac.jp
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sasaki
authors.forename: Mikio
authors.initials: M
authors.lastname: Shoji
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Harigaya
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kawarabayashi
authors.forename: Masaki
authors.initials: M
authors.lastname: Ikeda
authors.forename: Makoto
authors.initials: M
authors.lastname: Naito
authors.forename: Etsuro
authors.initials: E
authors.lastname: Matsubara
authors.forename: Koji
authors.initials: K
authors.lastname: Abe
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Nakazato
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology; D003224:Congo Red; D004195:Disease Models, Animal; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D007150:Immunohistochemistry; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D017628:Microglia / Q000378:metabolism* / Q000473:pathology; D016253:Microscopy, Immunoelectron; D016501:Neurites / Q000378:metabolism* / Q000473:pathology; D016874:Neurofibrillary Tangles / Q000378:metabolism* / Q000648:ultrastructure; D058225:Plaque, Amyloid / Q000378:metabolism* / Q000473:pathology; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000378:metabolism; D000097382:CD68 Molecule
chemical_list: D016564:Amyloid beta-Protein Precursor; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D003224:Congo Red; D000949:Histocompatibility Antigens Class II; D016177:Macrophage-1 Antigen; D016186:Receptor, Macrophage Colony-Stimulating Factor; C081026:CD68 protein, mouse; D000097382:CD68 Molecule