title: The neuritic plaque facilitates pathological conversion of tau in an Alzheimer's disease mouse model.
abstract: A central question in Alzheimer's Disease (AD) is whether the neuritic plaque is necessary and sufficient for the development of tau pathology. Hyperphosphorylation of tau is found within dystrophic neurites surrounding β-amyloid deposits in AD mouse models but the pathological conversion of tau is absent. Likewise, expression of a human tau repeat domain in mice is insufficient to drive the pathological conversion of tau. Here we developed an Aβ-amyloidosis mouse model that expresses the human tau repeat domain and show that in these mice, the neuritic plaque facilitates the pathological conversion of wild-type tau. We show that this tau fragment seeds the neuritic plaque-dependent pathological conversion of wild-type tau that spreads from the cortex and hippocampus to the brain stem. These results establish that in addition to the neuritic plaque, a second determinant is required to drive the conversion of wild-type tau.
authors.affiliation: Department of Pathology, The Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross 558, Baltimore, Maryland 21205, USA.
authors.forename: Tong
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Pathology, The Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross 558, Baltimore, Maryland 21205, USA.
authors.forename: Kerstin E
authors.initials: KE
authors.lastname: Braunstein
authors.affiliation: Department of Pathology, The Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross 558, Baltimore, Maryland 21205, USA.
authors.forename: Juhong
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Pathology, The Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross 558, Baltimore, Maryland 21205, USA.
authors.forename: Ashley
authors.initials: A
authors.lastname: Lau
authors.affiliation: Department of Pathology, The Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross 558, Baltimore, Maryland 21205, USA.
authors.forename: Leslie
authors.initials: L
authors.lastname: Sibener
authors.affiliation: Department of Pathology, The Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross 558, Baltimore, Maryland 21205, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Deeble
authors.affiliation: Department of Pathology, The Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross 558, Baltimore, Maryland 21205, USA.|Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Philip C
authors.initials: PC
authors.lastname: Wong
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005911:Gliosis / Q000473:pathology; D006801:Humans; D008297:Male; D008822:Mice, Transgenic; D008954:Models, Biological; D050505:Mutant Proteins / Q000737:chemistry / Q000378:metabolism; D016501:Neurites / Q000378:metabolism*; D010766:Phosphorylation; D058225:Plaque, Amyloid / Q000378:metabolism* / Q000473:pathology*; D016548:Prosencephalon / Q000473:pathology; D020449:Repetitive Sequences, Amino Acid; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D050505:Mutant Proteins; D016875:tau Proteins