UCL Research Department of Cell and Developmental Biology

Memory loss in Alzheimer's disease could be prevented by targeting a secreted protein that dismantles synapses

Alzheimer’s disease is characterized by abnormal deposits in the brain of the protein Amyloid-ß, which induces the loss of connections between neurons, called synapses. However, the mechanisms that induce synaptic loss are not understood.

Professor Patricia Salinas (UCL Department of Cell & Developmental Biology) and her research team have discovered that specific antibodies that block the function of a protein, called Dkk1, are able to completely suppress the toxic effect of Amyloid-ß on synapses. The findings are published in the Journal of Neuroscience.

Dkk1 is elevated in the brain biopsies of people with Alzheimer’s disease but the significance of these findings was previously unknown. Two members of the Salinas’ group, Drs Silvia Purro and Ellen Dickins, found that Amyloid-ß causes the rapid production of Dkk1, which in turn induces the dismantling of synapses (the connections between neurons) in the hippocampus, an area of the brain implicated in learning and memory. However, specific antibodies against Dkk1 could prevent synaptic loss induced by Amyloid-ß. Neurons that were exposed to the antibody remained healthy, with no synaptic disintegration.

Professor Salinas said: “Despite significant advances in understanding the molecular mechanisms involved in Alzheimer’s disease, no effective treatment is currently available to stop the progression of this devastating disease.” She added: “This research identifies Dkk1 as a potential therapeutic target for the treatment of Alzheimer’s disease.”

The research was funded by Alzheimer’s Research UK, the BBSRC and the Wellcome Trust.

Dr Simon Ridley, Head of Research at Alzheimer’s Research UK, said: “We’re delighted to have supported this study”. “Studies like this are an essential part of that process, but more work is needed if we are to take these results from the lab bench to the clinic. Dementia can only be defeated through research, and with the numbers of people affected by the condition soaring, we urgently need to invest in research now.”

More on this story:

The Journal of Neuroscience

UCL Press Release

The article at UCL News 

The BBSRC's coverage of the story

Article Image:

Amyloid beta (cyan blue) binds to nerve cells of the hippocampus (red) and attacks synapses resulting in the loss of memories in Alzheimer’s disease. New research has led to important insights into the mechanisms that induce synapse loss. The discovery brings hope for the development of new therapies that protect synapses and therefore prevent memory loss in Alzheimer’s disease.

Credit: Silvia Purro/Patricia Salinas/UCL