Katherine J Sellers, Christina Elliott, Joshua Jackson, Anshua Ghosh, Elena Ribe, Ana I Rojo, Heledd H Jarosz-Griffiths, Iain A Watson, Weiming Xia, Mikhail Semenov, Peter Morin, Nigel M Hooper, Rod Porter, Jane Preston, Raya Al-Shawi, George Baillie, Simon Lovestone, Antonio Cuadrado, Michael Harte, Paul Simons, Deepak P Srivastava, Richard Killick
INTRODUCTION: Synapse loss is the structural correlate of the cognitive decline indicative of dementia. In the brains of Alzheimer's disease sufferers, amyloid β (Aβ) peptides aggregate to form senile plaques but as soluble peptides are toxic to synapses. We previously demonstrated that Aβ induces Dickkopf-1 (Dkk1), which in turn activates the Wnt-planar cell polarity (Wnt-PCP) pathway to drive tau pathology and neuronal death. METHODS: We compared the effects of Aβ and of Dkk1 on synapse morphology and memory impairment while inhibiting or silencing key elements of the Wnt-PCP pathway...
March 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association