Synaptic loss is critical in Alzheimer's disease (AD), but the dynamics of synapse turnover are poorly defined. We imaged dendritic spines in transgenic APPswe/PSen1∆E9 (APP/PS1) cerebral cortex. Dendritic spine turnover is increased far from plaque in aged APP/PS1 mice, and in young APP/PS1 mice prior to plaque formation. Dysregulation occurs in the presence of soluble Aβ oligomer and requires cellular prion protein (PrPC). APP/PS1 mice lack responsiveness of spine turnover to sensory stimulation. Critically, enhanced spine turnover is coupled with the loss of persistent spines starting early and continuing with age. To evaluate mechanisms of experience-independent supranormal spine turnover, we analyzed the transcriptome of young APP/PS1 mouse brain when turnover is altered but synapse density and memory are normal, and plaque and inflammation are absent. Early PrPC-dependent expression changes occur in synaptic and lipid-metabolizing genes. Thus, pathologic synaptic dysregulation underlying AD begins at a young age prior to Aβ plaque.

Rural local governments across Canada, including those in Newfoundland and Labrador, struggle with many of their day‐to‐day operational activities, including providing appropriate drinking water, wastewater, and garbage collection services, among other essential services, and rarely have capacity to facilitate local economic development activities. In recent times, entrepreneurialism has been noted as having potential for rural local governments, yet little research has been completed to determine its presence and relevance for municipalities in Newfoundland and Labrador. In response, we examined eight case study local governments in Newfoundland and Labrador to determine if, and how, entrepreneurialism was present in municipal efforts to increase economic prosperity in their communities. Findings suggest that while rural local governments continue to face challenges due to declining support for rural development from provincial and federal governments and increased downloading of responsibilities, some communities have established ways to remain resilient through partnerships and building on place‐based assets. This exploratory study provides a basis for further in‐depth research to determine the extent and approaches to entrepreneurialism in local government in rural Newfoundland and Labrador.

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