Altered Synapse Stability in the Early Stages of Tauopathy
Johanna S. Jackson,
Jonathan Witton,
James D. Johnson,
Zeshan Ahmed,
Mark Ward,
Andrew D. Randall,
Michael L. Hutton,
John T. Isaac,
Michael J. O’Neill,
Michael C. Ashby
Affiliations
Johanna S. Jackson
Lilly UK, Erl Wood Manor, Windlesham, Surrey GU20 6PH, UK
Jonathan Witton
Centre for Synaptic Plasticity, School of Physiology, Pharmacology and Neuroscience, University of Bristol, Biomedical Sciences Building, University Walk, Bristol BS8 1TD, UK
James D. Johnson
Lilly UK, Erl Wood Manor, Windlesham, Surrey GU20 6PH, UK
Zeshan Ahmed
Lilly UK, Erl Wood Manor, Windlesham, Surrey GU20 6PH, UK
Mark Ward
Lilly UK, Erl Wood Manor, Windlesham, Surrey GU20 6PH, UK
Andrew D. Randall
Centre for Synaptic Plasticity, School of Physiology, Pharmacology and Neuroscience, University of Bristol, Biomedical Sciences Building, University Walk, Bristol BS8 1TD, UK
Michael L. Hutton
Lilly UK, Erl Wood Manor, Windlesham, Surrey GU20 6PH, UK
John T. Isaac
Lilly UK, Erl Wood Manor, Windlesham, Surrey GU20 6PH, UK
Michael J. O’Neill
Lilly UK, Erl Wood Manor, Windlesham, Surrey GU20 6PH, UK
Michael C. Ashby
Centre for Synaptic Plasticity, School of Physiology, Pharmacology and Neuroscience, University of Bristol, Biomedical Sciences Building, University Walk, Bristol BS8 1TD, UK
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.
