title: Altered Synapse Stability in the Early Stages of Tauopathy.
abstract: Synapse loss is a key feature of dementia, but it is unclear whether synaptic dysfunction precedes degenerative phases of the disease. Here, we show that even before any decrease in synapse density, there is abnormal turnover of cortical axonal boutons and dendritic spines in a mouse model of tauopathy-associated dementia. Strikingly, tauopathy drives a mismatch in synapse turnover; postsynaptic spines turn over more rapidly, whereas presynaptic boutons are stabilized. This imbalance between pre- and post-synaptic stability coincides with reduced synaptically driven neuronal activity in pre-degenerative stages of the disease.
authors.affiliation: Lilly UK, Erl Wood Manor, Windlesham, Surrey GU20 6PH, UK.
authors.forename: Johanna S
authors.initials: JS
authors.lastname: Jackson
authors.affiliation: Centre for Synaptic Plasticity, School of Physiology, Pharmacology and Neuroscience, University of Bristol, Biomedical Sciences Building, University Walk, Bristol BS8 1TD, UK.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Witton
authors.affiliation: Lilly UK, Erl Wood Manor, Windlesham, Surrey GU20 6PH, UK; Centre for Synaptic Plasticity, School of Physiology, Pharmacology and Neuroscience, University of Bristol, Biomedical Sciences Building, University Walk, Bristol BS8 1TD, UK.
authors.forename: James D
authors.initials: JD
authors.lastname: Johnson
authors.affiliation: Lilly UK, Erl Wood Manor, Windlesham, Surrey GU20 6PH, UK.
authors.forename: Zeshan
authors.initials: Z
authors.lastname: Ahmed
authors.affiliation: Lilly UK, Erl Wood Manor, Windlesham, Surrey GU20 6PH, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Ward
authors.affiliation: Centre for Synaptic Plasticity, School of Physiology, Pharmacology and Neuroscience, University of Bristol, Biomedical Sciences Building, University Walk, Bristol BS8 1TD, UK.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Randall
authors.affiliation: Lilly UK, Erl Wood Manor, Windlesham, Surrey GU20 6PH, UK.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Hutton
authors.affiliation: Lilly UK, Erl Wood Manor, Windlesham, Surrey GU20 6PH, UK.
authors.forename: John T
authors.initials: JT
authors.lastname: Isaac
authors.affiliation: Lilly UK, Erl Wood Manor, Windlesham, Surrey GU20 6PH, UK.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: O'Neill
authors.affiliation: Centre for Synaptic Plasticity, School of Physiology, Pharmacology and Neuroscience, University of Bristol, Biomedical Sciences Building, University Walk, Bristol BS8 1TD, UK. Electronic address: m.c.ashby@bristol.ac.uk.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Ashby
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism; D002540:Cerebral Cortex / Q000473:pathology; D049229:Dendritic Spines / Q000378:metabolism; D008297:Male; D008822:Mice, Transgenic; D017729:Presynaptic Terminals / Q000378:metabolism; D013569:Synapses / Q000473:pathology*; D024801:Tauopathies / Q000473:pathology*
keywords: 2-photon microscopy; axon; bouton; cortex; dementia; dendritic spine; neurodegeneration