Researchers at the University of British Columbia have successfully reversed an apparent cause of Alzheimer’s disease by immunizing mice with a protein fragment closely associated with the development of the disease.
Mice and humans with Alzheimer’s show an abnormal increase in the concentration of blood vessels in the brain, as well as protein plaques that kill neurons.
But mice immunized with amyloid beta showed a reduction in the number of blood vessels to near normal levels and a reduction in plaques in the brain, according to the study published online in Scientific Reports, a Nature journal.
“The immunization definitely reverses the formation of amyloid plaques and at the same time it reverses the new formation of blood vessels,” said lead researcher Wilfred Jefferies, a professor in UBC’s Michael Smith Laboratories.
Human immunization trials in Sweden, the United Kingdom and the United States have shown that amyloid beta vaccines reduce plaques in the brain, but the trials have been fraught with medical complications and the mechanisms for the effect were unclear.
Jefferies’ discovery suggests that existing drugs designed to inhibit abnormal blood vessel growth could be used to treat or prevent Alzheimer’s disease, which accounts for two thirds of all dementia cases.
Drugs that target abnormal growth of blood vessels – such as wet macular degeneration – could be useful against Alzheimer’s, Jefferies said.
Amyloid beta protein, which forms damaging plaques in the brains of Alzheimer’s patients, is also widely believed to be a probable cause of the disease, though its role has never been well understood.
The study is the second by Jefferies that implicates abnormal growth of blood vessels as a potential cause of Alzheimer’s.
In a 2011 study, Jefferies found that an overabundance of blood vessels in Alzheimer’s patients and in mice with the disease appeared to compromise the blood-brain barrier, allowing amyloid beta protein fragments to cross and accumulate on neurons, eventually killing them.
Jefferies found that humans and mice with Alzheimer’s have nearly double the number of capillaries – tiny blood vessels that deliver oxygen and nutrients – in their brains.
Previous studies assumed that blood vessel death was behind damage to the blood-brain barrier. But Jefferies suggested that amyloid beta stimulates the abnormal growth of blood vessels, rather than killing them.
The blood-brain barrier is a tightly woven membrane that prevents even the tiniest pathogens and viruses from getting into the brain. But when the blood vessels in the brain are abnormally stimulated to grow, the newly grown cells are not immediately the right shape, creating a leaky membrane and allowing harmful proteins to attack the brain, according to Jefferies.
By injecting mice with small amounts of amyloid beta in the most recent study, Jefferies was able to stimulate a natural immune response against the protein, clearing it from the bloodstream, reducing the abnormal growth of blood vessels and reversing the growth of damaging protein plaques in the brain.
The study was done in collaboration with researchers at UBC’s Biomedical Research Centre and Mount Sinai School of Medicine in New York.
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