Specific antibodies halt Alzheimer’s disease in mice
6 March 2012
that block the process of synapse disintegration in Alzheimer’s disease have
been identified, 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-ß, which induces the loss of connections between neurons,
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-ß on synapses. The findings are published today in the
Journal of Neuroscience.
Professor Patricia Salinas (UCL Department of Cell & Developmental
Biology) who led the study, said: “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-ß.
“Importantly, these results raise the hope for a treatment and perhaps the
prevention of cognitive decline early in Alzheimer’s disease.”
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-ß 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.
Importantly, these results raise the hope for a treatment and perhaps the prevention of cognitive decline early in Alzheimer’s disease.
Professor Patricia Salinas
In this paper, scientists conducted experiments to look at the progression of
synapse disintegration of the hippocampus after exposure to Amyloid-ß, 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.
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.”
Alzheimer’s represents 60% of all cases of dementia. Alzheimer’s Research UK
estimates that in the UK the annual national cost of all the dementias is
around £23 billion, which represents double the costs for cancer and 3-5 times
the costs for heart disease and stroke.
New studies predict an increase in the
number of Alzheimer’s cases of epidemic proportions.
The research was funded by Alzheimer’s Research UK, the UK’s leading dementia
research charity, and the Biotechnology and Biological Sciences Research
Dr Simon Ridley, Head of Research at Alzheimer’s Research UK, said: “We’re
delighted to have supported this study, which sheds new light on the processes
that occur as Alzheimer’s develops. By understanding what happens in the brain
during Alzheimer’s, we stand a better chance of developing new treatments that
could make a real difference to people with the disease.
“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.”
Media Contact: Clare Ryan
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