title: Immunohistochemical detection of the delayed formation of nonfibrillar large amyloid-β aggregates.
abstract: The occurrence of senile plaques consisting of amyloid-β protein (Aβ) is a major neuropathological hallmark of Alzheimer's disease (AD). We previously developed and characterized monoclonal antibodies 31-2 and 75-2 that specifically bind to nonfibrillar Aβ1-42 aggregates with diameters of more than 220 and 50 nm, respectively. Here, we report the use of these antibodies to examine the aggregation of exogenous Aβ1-42 in cultured rat hippocampal neurons. From 6 to 24 h after transfection of Aβ1-42, antibody 75-2 immunolabeled almost all transfected neurons, whereas 31-2-positive cells were restricted to a part of the transfected neurons and gradually increased in number. Expression of the F19S/L34P-mutant Aβ1-42, which showed less of a tendency to aggregate, resulted in clearly reduced immunoreactivity to both antibodies. We also immunohistochemically investigated the temporal cortices of patients with AD and found that 31-2 preferentially labeled the cores of a subpopulation of large amyloid plaques. The relative number of 31-2-immunoreactive plaques was found to correlate with the Braak stages of neurofibrillary tangles, but not with that of amyloid plaques. These results suggest that 31-2-reactive Aβ aggregates develop with a delayed time course in cultured neurons and amyloid plaques of AD brains.
authors.affiliation: Biomedical Research Institute, DAILAB, National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Higashi, Tsukuba, Ibaraki, 305-8566, Japan.
authors.forename: Tomoyo
authors.initials: T
authors.lastname: Ochiishi
authors.affiliation: Department of Applied Molecular Chemistry, Graduate School of Industrial Technology, Nihon University, 1-2-1, Izumichou, Narashino, Chiba, 275-8575, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Itakura
authors.affiliation: Molecular Neuroscience Research Center, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga, 520-2192, Japan.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: Choju Medical Institute, Fukushimura Hospital, 19-14, Aza-Yamanaka, Noyori, Toyohashi, Aichi, 441-8124, Japan.|Department of Medicine for Aging in Place and Community-Based Medical Education, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, 466-8550, Japan.
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Akatsu
authors.affiliation: Hoshi University, 2-4-41, Ebara, Shinagawa, Tokyo, 142-8501, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Kohno
authors.affiliation: Molecular Neuroscience Research Center, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga, 520-2192, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Nishimura
authors.affiliation: Department of Applied Molecular Chemistry, Graduate School of Industrial Technology, Nihon University, 1-2-1, Izumichou, Narashino, Chiba, 275-8575, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Yoshimune
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000276:immunology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D006624:Hippocampus / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009154:Mutation; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D016229:Amyloid beta-Peptides; D000911:Antibodies, Monoclonal