title: Synaptic Contacts Enhance Cell-to-Cell Tau Pathology Propagation.
abstract: Accumulation of insoluble Tau protein aggregates and stereotypical propagation of Tau pathology through the brain are common hallmarks of tauopathies, including Alzheimer's disease (AD). Propagation of Tau pathology appears to occur along connected neurons, but whether synaptic contacts between neurons are facilitating propagation has not been demonstrated. Using quantitative in vitro models, we demonstrate that, in parallel to non-synaptic mechanisms, synapses, but not merely the close distance between the cells, enhance the propagation of Tau pathology between acceptor hippocampal neurons and Tau donor cells. Similarly, in an artificial neuronal network using microfluidic devices, synapses and synaptic activity are promoting neuronal Tau pathology propagation in parallel to the non-synaptic mechanisms. Our work indicates that the physical presence of synaptic contacts between neurons facilitate Tau pathology propagation. These findings can have implications for synaptic repair therapies, which may turn out to have adverse effects by promoting propagation of Tau pathology.
authors.affiliation: Neuroscience Department, Janssen Research and Development, a Division of Janssen Pharmaceutica NV, 2340 Beerse, Belgium; VIB Center for the Biology of Disease, 3000 Leuven, Belgium; KU Leuven Department for Human Genetics, 3000 Leuven, Belgium.
authors.forename: Sara
authors.initials: S
authors.lastname: Calafate
authors.affiliation: Neuroscience Department, Janssen Research and Development, a Division of Janssen Pharmaceutica NV, 2340 Beerse, Belgium.
authors.forename: Arjan
authors.initials: A
authors.lastname: Buist
authors.affiliation: VIB Center for the Biology of Disease, 3000 Leuven, Belgium; KU Leuven Department for Human Genetics, 3000 Leuven, Belgium.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Miskiewicz
authors.affiliation: VIB Center for the Biology of Disease, 3000 Leuven, Belgium; KU Leuven Department for Human Genetics, 3000 Leuven, Belgium.
authors.forename: Vinoy
authors.initials: V
authors.lastname: Vijayan
authors.affiliation: Neuroscience Department, Janssen Research and Development, a Division of Janssen Pharmaceutica NV, 2340 Beerse, Belgium.
authors.forename: Guy
authors.initials: G
authors.lastname: Daneels
authors.affiliation: VIB Center for the Biology of Disease, 3000 Leuven, Belgium; KU Leuven Department for Human Genetics, 3000 Leuven, Belgium.
authors.forename: Bart
authors.initials: B
authors.lastname: de Strooper
authors.affiliation: VIB Center for the Biology of Disease, 3000 Leuven, Belgium; KU Leuven Department for Human Genetics, 3000 Leuven, Belgium.
authors.forename: Joris
authors.initials: J
authors.lastname: de Wit
authors.affiliation: VIB Center for the Biology of Disease, 3000 Leuven, Belgium; KU Leuven Department for Human Genetics, 3000 Leuven, Belgium. Electronic address: patrik.verstreken@cme.vib-kuleuven.be.
authors.forename: Patrik
authors.initials: P
authors.lastname: Verstreken
authors.affiliation: Neuroscience Department, Janssen Research and Development, a Division of Janssen Pharmaceutica NV, 2340 Beerse, Belgium. Electronic address: dmoechar@its.jnj.com.
authors.forename: Diederik
authors.initials: D
authors.lastname: Moechars
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000502:physiology*; D018450:Disease Progression; D057809:HEK293 Cells; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D006801:Humans; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000378:metabolism / Q000473:pathology*; D024801:Tauopathies / Q000378:metabolism / Q000473:pathology*; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016875:tau Proteins