Researchers Preserve Memory of Mice with Possible New Alzheimer’s Vaccine

With no cure for Alzheimer’s disease, there have been attempts to develop vaccinations against it. A new study may have found a new approach for one.

Researchers at the University of Kansas took a recombinant methionine (Met)-rich protein derived from corn to produce the antigen methionine sulfoxide (MetO)-rich protein. They investigated whether this antigen could be used to mount an immune system attack against beta-amyloid and improve memory in mice with Alzheimer’s disease. Their study results, published in the journal Antioxidants, show promise.

Jackob Moskovitz, lead researcher and associate professor of pharmacology and toxicology at the KU School of Pharmacy, says, “As we age, we have more oxidative stress, and then beta-amyloid and other proteins accumulate and become oxidized and aggregated – these proteins are resistant to degradation or removal. In a previous 2011 published study, I injected mouse models of Alzheimer’s disease with a similar methionine sulfoxide-rich protein and showed about 30% reduction of amyloid plaque burden in the hippocampus, the main region where damage from Alzheimer’s disease occurs.”

The researchers say this works because the antigen helps activate the immune system to produce antibodies against the MetO component of beta-amyloid, which is a trademark of Alzheimer’s disease that is toxic to brain cells. The process leads to a reduced level of toxic forms of beta-amyloid and other proteins in the brain.

In this study, the team injected the MetO-rich protein into 4-month-old mice that had been genetically modified to develop the familial form of Alzheimer’s. Through followup testing, they found that the antigen prompted the mice’s immune systems to produce antibodies that worked against Alzheimer’s phenotypes until at least 10 months of age.

The team also tested the memories of injected and non-injected mice, finding that there was a roughly 50% memory improvement in the first group.

Moskovitz says, “We measured short-term memory capability through a ‘Y’ maze, and that’s very important in Alzheimer’s disease — because when people get Alzheimer’s, their short-term memory is going away, while the old memories are still there. You put a mouse in a maze shaped like a ‘Y’ so they can go either the left or right arm. But then you introduce a third arm in the middle and if they recognize the third arm as new, they’ll spend more time exploring that new arm because they have curiosity. If they don’t even notice there’s a third arm — because they forget it the minute after they saw it — they will spend more time in right or left.”

In an experiment that required the mice to find a platform in a water maze, the injected mice also accomplished the task much faster than the control group. When the team removed the platform, the vaccinated mice were also more apt to spend time where it had been after it disappeared.

Additionally, the study showed that being immunized with the antigen led to better longterm memory capacity, reduced beta-amyloid levels in blood-plasma and the brain, and better health in the hippocampal and cortical regions.

Going forward, the team hopes to be able to do trials in humans. Ultimately, if the immunization were successful, Moskovitz says it could be administered to people in their 50s or 60s, who could then receive intermittent booster doses.