A new vaccine prevents the development of Alzheimer's disease in mice, without causing significant side effects.
The vaccine given to the mice provoked an immune response to the protein known as amyloid-beta peptide, which accumulates in what are called "amyloid plaques" in the brains of those with Alzheimer's. Vaccinated were tested and found to have normal learning and memory skills in spite of being genetically designed to develop an aggressive form of the disease.
University of Rochester Medical Center scientists reported the findings in the May 2008 issue of Molecular Therapy, the journal of The American Society of Gene Therapy.
"Our study demonstrates that we can create a potent but safe version of a vaccine that utilizes the strategy of immune response shaping to prevent Alzheimer's-related pathologies and memory deficits," said William Bowers, associate professor of neurology and of microbiology and immunology at the Medical Center and lead author of the article. "The vaccinated mice not only performed better, we found no evidence of signature amyloid plaque in their brains."
Alzheimer's is a progressive disease associated with dementia. Hallmarks of the disease include the accumulation of amyloid plaques in the brains of patients and the loss of normal functioning tau, a protein that stabilizes the transport networks in neurons. These neurons eventually succumb and die, damaging learning and memory centers in the brain.
The mice that received the vaccines were genetically engineered to express large amounts of amyloid beta protein. Before the start of the vaccine study, the mice were trained to navigate a maze using spatial clues. They were then tested periodically during the 10-month study on the amount of time and distance traveled to an escape pod and the number of errors made along the way.
"What we found exciting was that by targeting one pathology of Alzheimer's — amyloid beta — we were able to also prevent the transition of tau from its normal form to a form found in the disease state," Bowers said.
The researchers' idea was to prompt the immune system to recognize amyloid beta protein and attack it. They tested several versions of a vaccine before finding the right one.
"We have learned a great deal from this ongoing project," Bowers said. "Importantly, it has demonstrated the combined strengths of the gene delivery platform and the immune shaping concept for the creation of customized vaccines for Alzheimer's disease, as well as a number of other diseases. We are currently working on strategies we believe can make the vaccine even safer."
Bowers expects that it could be three or more years before human trials testing this type of Alzheimer's vaccine occur.
