title: Spreading of pathology in neurodegenerative diseases: a focus on human studies.
abstract: The progression of many neurodegenerative diseases is thought to be driven by the template-directed misfolding, seeded aggregation and cell-cell transmission of characteristic disease-related proteins, leading to the sequential dissemination of pathological protein aggregates. Recent evidence strongly suggests that the anatomical connections made by neurons - in addition to the intrinsic characteristics of neurons, such as morphology and gene expression profile - determine whether they are vulnerable to degeneration in these disorders. Notably, this common pathogenic principle opens up opportunities for pursuing novel targets for therapeutic interventions for these neurodegenerative disorders. We review recent evidence that supports the notion of neuron-neuron protein propagation, with a focus on neuropathological and positron emission tomography imaging studies in humans.
authors.affiliation: 1] Center for Neurodegenerative Disease Research, Perelman School of Medicine at the University of Pennsylvania, 3rd Floor Maloney Building, 3400 Spruce Street, Philadelphia, Pennsylvania 19104, USA. [2] Clinical Neuroanatomy Section, Department of Neurology, Center for Biomedical Research, University of Ulm, Helmholtzstrasse 8/1, 89081 Ulm, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Brettschneider
authors.affiliation: Clinical Neuroanatomy Section, Department of Neurology, Center for Biomedical Research, University of Ulm, Helmholtzstrasse 8/1, 89081 Ulm, Germany.
authors.forename: Kelly
authors.initials: K
authors.lastname: Del Tredici
authors.affiliation: 1] Center for Neurodegenerative Disease Research, Perelman School of Medicine at the University of Pennsylvania, 3rd Floor Maloney Building, 3400 Spruce Street, Philadelphia, Pennsylvania 19104, USA. [2] Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, 3rd Floor Maloney Building, 3400 Spruce Street, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Virginia M-Y
authors.initials: VM
authors.lastname: Lee
authors.affiliation: 1] Center for Neurodegenerative Disease Research, Perelman School of Medicine at the University of Pennsylvania, 3rd Floor Maloney Building, 3400 Spruce Street, Philadelphia, Pennsylvania 19104, USA. [2] Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, 3rd Floor Maloney Building, 3400 Spruce Street, Philadelphia, Pennsylvania 19104, USA.
authors.forename: John Q
authors.initials: JQ
authors.lastname: Trojanowski
mesh_terms: D001921:Brain / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D006801:Humans; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000473:pathology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology*