Altered synapse stability in the early stages of tauopathy
Elsevier (Cell Press)
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 stablised. This imbalance between pre- and post-synaptic stability coincides with reduced synaptically- driven neuronal activity in pre-degenerative stages of the disease.
J.D.J. is funded by a BBSRC CASE PhD studentship. Experiments completed in M.C.A.’s laboratory were funded by an MRC centenary award and ARUK Research Fellowship ( ARUK-RF2015-6 ) to J.W., Alzheimer’s Research UK ( ARUK-ESG2014-3 ), the Medical Research Council ( MR/J013188/1 ), and EUFP7 Marie Curie Actions ( PCIG10-GA-2011-303680 ). The authors would like to thank Anna Gawedzka, who helped with the image analysis; Jane Cooper, who assisted with the structural imaging; and the University of Bristol Statistics Helpdesk for advice on mixed-model statistical approaches.
This is the author accepted manuscript. The final version is freely available from Elsevier (Cell Press) via the DOI in this record.
Vol.18, Iss. 13, pp. 3063–3068