title: Microglial activation in brain lesions with tau deposits: comparison of human tauopathies and tau transgenic mice TgTauP301L.
abstract: The aim of this study is to clarify the relationship of microglia to phosphorylated tau accumulation and the characteristics of microglial activation in brain lesions of human tauopathies in comparison to mutant tau transgenic (TG) mice. We performed immunocytochemical analyses of brains from six patients with tauopathies, and 24 mice (18 TG mice expressing mutant tau P301L and six non-TG control mice, 11 to 27 months of age) using anti-tau antibodies and various microglial markers. In the tau TG, both semiquantitative severity ratings of microglial activation and an ultrastructural study were performed. In human tauopathies, Iba1- and major histocompatibility complex (MHC) class II-positive activated microglia increased in regions of phosphorylated tau (AT8) accumulation. The immunoreactivity of scavenger receptor class A (SRA) was present in some activated microglia, including phagocytic microglia in Alzheimer's disease (AD). Double-immunofluorescent analysis under a confocal microscope showed activated microglia at the vicinity of AT8-positive cells. Semiquantitative data of the TG and control mice indicated that the immunopositivity of AT8 was closely associated with the number of Iba1-positive microglia in the cortical area. Tau-associated microglia showed rare immunoreactivity for MHC class II antigen and SRA in the TG mice. Ultrastructurally, activated microglia with enlarged cytoplasm were located near neurons containing abnormal cytoskeletons. This comparative study of human tauopathies and tau TG mice indicated that microglial activation was closely related to phosphorylated tau accumulation, and that activated microglia of the TG mice may have the low expression of MHC class II and SRA compared with those of human tauopathies.
authors.affiliation: Department of Human Pathology, Gunma University Graduate School of Medicine, Gunma, Japan. achie@med.gunma-u.ac.jp
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sasaki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kawarabayashi
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Murakami
authors.forename: Etsuro
authors.initials: E
authors.lastname: Matsubara
authors.forename: Masaki
authors.initials: M
authors.lastname: Ikeda
authors.forename: Haruo
authors.initials: H
authors.lastname: Hagiwara
authors.forename: David
authors.initials: D
authors.lastname: Westaway
authors.forename: Peter S
authors.initials: PS
authors.lastname: George-Hyslop
authors.forename: Mikio
authors.initials: M
authors.lastname: Shoji
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Nakazato
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D007930:Leucine / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008840:Microfilament Proteins; D017628:Microglia / Q000378:metabolism* / Q000648:ultrastructure; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D009154:Mutation; D011392:Proline / Q000235:genetics; D051116:Receptors, Scavenger / Q000378:metabolism; D024801:Tauopathies / Q000235:genetics / Q000473:pathology*; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C112986:AIF1 protein, human; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D000949:Histocompatibility Antigens Class II; D008840:Microfilament Proteins; D051116:Receptors, Scavenger; D016875:tau Proteins; D011392:Proline; D007930:Leucine