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Potential therapeutic target for treatment of Alzheimer's identified


March 7, 2012 - Washington

Scientists have identified antibodies that block the process of synapse disintegration in Alzheimer's disease, raising hopes for a treatment to combat early cognitive decline in the disease.

Alzheimer's disease is characterized by abnormal deposits in the brain of the protein Amyloid-beta , which induces the loss of connections between neurons, called synapses.

Now, scientists at UCL have discovered that specific antibodies that block the function of a related protein, called Dkk1, are able to completely suppress the toxic effect of Amyloid-beta on synapses.

"These novel findings raise the possibility that targeting this secreted Dkk1 protein could offer an effective treatment to protect synapses against the toxic effect of Amyloid-beta," said Dr Patricia Salinas, from the UCL Department of Cell and Developmental Biology, who led the study.

"Importantly, these results raise the hope for a treatment and perhaps the prevention of cognitive decline early in Alzheimer's disease," she stated.

Dkk1 is elevated in the brain biopsies of people with Alzheimer's disease but the significance of these findings was previously unknown. Scientists at UCL have found that Amyloid-beta causes the 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.

The scientists conducted experiments to look at the progression of synapse disintegration of the hippocampus after exposure to Amyloid-beta, using brain slices from mice.

They were able to monitor how many synapses survived in the presence of a specific antibody, which targets Dkk1, compared to how many synapses were viable without the antibody.

The results show that the neurons that were exposed to the antibody remained healthy, with no synaptic disintegration.

"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," noted Dr Salinas.

"This research identifies Dkk1 as a potential therapeutic target for the treatment of Alzheimer's disease," she added.

The findings have been published in the Journal of Neuroscience.

ANI

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