Principal Investigators


Patricia Salinas

Institution


University College London

Contact information of lead PI


Country


United Kingdom

Title of project or programme


The role of Dkk1 in Amyloid-beta mediated effects on dendritic spines and long-term depression

Source of funding information


Alzheimer's Research UK

Total sum awarded (Euro)


€ 539,478

Start date of award


02/07/2012

Total duration of award in years


4.0

The project/programme is most relevant to:


Alzheimer's disease & other dementias

Keywords


Research Abstract


Brain function depends on the formation of functional neuronal circuits created by connecting nerve cells together through specific junctions, called synapses. Loss or dysfunction of synapses contributes to diverse neurological disorders. Recent studies have revealed that synapse loss occurs at early stages of Alzheimer’s disease (AD) and that this process might contribute to cognitive and memory deficits in AD. Our research group studies the function of Wnts, proteins that promote the formation, growth and maintenance of synapses. We discovered that a secreted Wnt antagonist, Dkk1, induces synaptic loss and deficits in long-term memory in mice expressing high levels of Dkk1. Dkk1 is elevated in AD brain and in mouse models of AD. Importantly, we found that Amyloid ß (Aß) rapidly increases Dkk1 levels and that Dkk1 blockade suppresses the synaptic effects of Aß. Thus, Dkk1 is necessary for Aß-induced synapse loss and therefore Dkk1 may contribute to cognitive decline in AD. In this proposal, we will investigate the contribution of Dkk1 to Aß-mediated synaptic changes in the hippocampus, a brain area important for learning and memory. We will also screen for small molecules that modulate Wnt signalling with the aim to identify new therapeutic avenues for the treatment of AD.

Lay Summary


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