title: High-Molecular-Weight Paired Helical Filaments from Alzheimer Brain Induces Seeding of Wild-Type Mouse Tau into an Argyrophilic 4R Tau Pathology in Vivo.
abstract: In Alzheimer disease, the development of tau pathology follows neuroanatomically connected pathways, suggesting that abnormal tau species might recruit normal tau by passage from cell to cell. Herein, we analyzed the effect of stereotaxic brain injection of human Alzheimer high-molecular-weight paired helical filaments (PHFs) in the dentate gyrus of wild-type and mutant tau THY-Tau22 mice. After 3 months of incubation, wild-type and THY-Tau22 mice developed an atrophy of the dentate gyrus and a tau pathology characterized by Gallyas and tau-positive grain-like inclusions into granule cells that extended in the hippocampal hilus and eventually away into the alveus, and the fimbria. Gallyas-positive neuropil threads and oligodendroglial coiled bodies were also observed. These tau inclusions were composed only of mouse tau, and were immunoreactive with antibodies to 4R tau, phosphotau, misfolded tau, ubiquitin, and p62. Although local hyperphosphorylation of tau was increased in the dentate gyrus in THY-Tau22 mice, the development of neurofibrillary tangles made of mutant human tau was not accelerated in the hippocampus, indicating that wild-type human PHFs were inefficient in seeding tau aggregates made of G272V/P301S mutant human tau. Our results indicate thus that injection of human wild-type Alzheimer PHF seeded aggregation of wild-type murine tau into an argyrophilic 4R tau pathology, and constitutes an interesting model independent of expression of a mutant tau protein.
authors: Laboratory of Histology, Neuroanatomy and Neuropathology, Faculty of Medicine, Université Libre de Bruxelles, ULB Neuroscience Institute, Brussels, Belgium.
authors: Emilie
authors: E
authors: Audouard
authors: Laboratory of Histology, Neuroanatomy and Neuropathology, Faculty of Medicine, Université Libre de Bruxelles, ULB Neuroscience Institute, Brussels, Belgium.
authors: Sarah
authors: S
authors: Houben
authors: Laboratory of Histology, Neuroanatomy and Neuropathology, Faculty of Medicine, Université Libre de Bruxelles, ULB Neuroscience Institute, Brussels, Belgium.
authors: Caterina
authors: C
authors: Masaracchia
authors: Laboratory of Histology, Neuroanatomy and Neuropathology, Faculty of Medicine, Université Libre de Bruxelles, ULB Neuroscience Institute, Brussels, Belgium.
authors: Zehra
authors: Z
authors: Yilmaz
authors: Laboratory of Histology, Neuroanatomy and Neuropathology, Faculty of Medicine, Université Libre de Bruxelles, ULB Neuroscience Institute, Brussels, Belgium.
authors: Valérie
authors: V
authors: Suain
authors: Laboratory of Histology, Neuroanatomy and Neuropathology, Faculty of Medicine, Université Libre de Bruxelles, ULB Neuroscience Institute, Brussels, Belgium.
authors: Michèle
authors: M
authors: Authelet
authors: Laboratory of Histology, Neuroanatomy and Neuropathology, Faculty of Medicine, Université Libre de Bruxelles, ULB Neuroscience Institute, Brussels, Belgium.
authors: Robert
authors: R
authors: De Decker
authors: INSERM, U837, Université de Lille 2, Lille, France.
authors: Luc
authors: L
authors: Buée
authors: Laboratory of Histology, Neuroanatomy and Neuropathology, Faculty of Medicine, Université Libre de Bruxelles, ULB Neuroscience Institute, Brussels, Belgium.
authors: Alain
authors: A
authors: Boom
authors: Laboratory of Histology, Neuroanatomy and Neuropathology, Faculty of Medicine, Université Libre de Bruxelles, ULB Neuroscience Institute, Brussels, Belgium.
authors: Karelle
authors: K
authors: Leroy
authors: Laboratory of Histology, Neuroanatomy and Neuropathology, Faculty of Medicine, Université Libre de Bruxelles, ULB Neuroscience Institute, Brussels, Belgium.
authors: Kunie
authors: K
authors: Ando
authors: Laboratory of Histology, Neuroanatomy and Neuropathology, Faculty of Medicine, Université Libre de Bruxelles, ULB Neuroscience Institute, Brussels, Belgium. Electronic address: jpbrion@ulb.ac.be.
authors: Jean-Pierre
authors: JP
authors: Brion
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000378:metabolism / Q000473:pathology; D016466:CHO Cells; D003412:Cricetulus; D003599:Cytoskeleton / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology*; D020033:Protein Isoforms; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C558298:Mapt protein, mouse; D020033:Protein Isoforms; D016875:tau Proteins