title: 3D Visualization of the Temporal and Spatial Spread of Tau Pathology Reveals Extensive Sites of Tau Accumulation Associated with Neuronal Loss and Recognition Memory Deficit in Aged Tau Transgenic Mice.
abstract: 3D volume imaging using iDISCO+ was applied to observe the spatial and temporal progression of tau pathology in deep structures of the brain of a mouse model that recapitulates the earliest stages of Alzheimer's disease (AD). Tau pathology was compared at four timepoints, up to 34 months as it spread through the hippocampal formation and out into the neocortex along an anatomically connected route. Tau pathology was associated with significant gliosis. No evidence for uptake and accumulation of tau by glia was observed. Neuronal cells did appear to have internalized tau, including in extrahippocampal areas as a small proportion of cells that had accumulated human tau protein did not express detectible levels of human tau mRNA. At the oldest timepoint, mature tau pathology in the entorhinal cortex (EC) was associated with significant cell loss. As in human AD, mature tau pathology in the EC and the presence of tau pathology in the neocortex correlated with cognitive impairment. 3D volume imaging is an ideal technique to easily monitor the spread of pathology over time in models of disease progression.
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, New York, United States of America.|Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York, United States of America.
authors.forename: Hongjun
authors.initials: H
authors.lastname: Fu
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, New York, United States of America.|Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York, United States of America.
authors.forename: S Abid
authors.initials: SA
authors.lastname: Hussaini
authors.affiliation: Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, United States of America.
authors.forename: Susanne
authors.initials: S
authors.lastname: Wegmann
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, New York, United States of America.|Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York, United States of America.
authors.forename: Caterina
authors.initials: C
authors.lastname: Profaci
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, New York, United States of America.|Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York, United States of America.
authors.forename: Jacob D
authors.initials: JD
authors.lastname: Daniels
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, New York, United States of America.|Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York, United States of America.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Herman
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, New York, United States of America.|Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York, United States of America.
authors.forename: Sheina
authors.initials: S
authors.lastname: Emrani
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, New York, United States of America.|Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York, United States of America.
authors.forename: Helen Y
authors.initials: HY
authors.lastname: Figueroa
authors.affiliation: Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, United States of America.
authors.forename: Bradley T
authors.initials: BT
authors.lastname: Hyman
authors.affiliation: Litwin-Zucker Center for Research in Alzheimer's Disease, Feinstein Institute for Medical Research, North Shore/LIJ Health System, Manhasset, New York, United States of America.
authors.forename: Peter
authors.initials: P
authors.lastname: Davies
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, New York, United States of America.|Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York, United States of America.
authors.forename: Karen E
authors.initials: KE
authors.lastname: Duff
mesh_terms: D000818:Animals; D005911:Gliosis / Q000378:metabolism; D006801:Humans; D008569:Memory Disorders / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism*; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D016875:tau Proteins