Researchers have discovered a direct relationship between two specific antibodies and the severity of Alzheimer's symptoms, raising hopes for the possibility of a diagnostic blood test for the disease.

The researchers compared antibody levels in blood samples from 118 older adults with the participant's level of dementia. They found that the concentration of two specific proteins that are involved in the immune response increases as the severity of dementia increases.

"We found a strong and consistent relationship between two particular antibodies and the level of impairment," said study co-author L. Stephen Miller. "The finding brings us closer to our ultimate goal of developing a blood test that can diagnose Alzheimer's or potentially identify if someone is at higher risk for the disease."

The research team focused on antibodies that the body creates in response to two proteins that are associated with Alzheimer's. One protein, known as amyloid-beta, forms the plaques that are evident in the brains of people with Alzheimer's upon autopsy. The other protein, known as RAGE, is involved in the normal aging process but is expressed at higher levels in the brains of people with Alzheimer's.

In a previous study that compared a group of people with Alzheimer's disease to a healthy control group, it was found that anti-amyloid beta and anti-RAGE antibodies are significantly higher in the group with Alzheimer's. The team's latest study expands on that finding to reveal a direct relationship between severity of Alzheimer's and levels of the two antibodies in the blood.

Alzheimer's is an inflammatory disease of the brain, and these two antibodies give us a way to measure that inflammation," said Shyamala Mruthinti, study co-author. "Using them as an early diagnostic marker may allow us to start treatment early, when it's most effective, to increase the patient's quality of life.

The researchers caution that it could still be years before a diagnostic test based on their work is clinically available. The study found that the relationship between the two antibodies and Alzheimer's severity persists even after controlling for patient age and total antibody levels. To further test the strength of the relationship, the researchers are now working with a sample that controls for other factors that have the potential to influence levels of the two antibodies, such as diabetes and heart disease.

"We're in the process of trying to reduce the test to a one-day procedure, whereas right now it takes three to four days," said Jerry Buccafusco, director of the MCG Alzheimer's Research Center. "But even now, our test is orders of magnitude cheaper than having people come in every few months to get a functional MRI or PET scan to try to discern brain plaques."

The team is targeting the two proteins themselves as a possible treatment for Alzheimer's. Mruthinti explains that, individually, amyloid-beta and RAGE proteins don't provoke an immune response. The trouble begins when the two bind and the immune system attacks, resulting in constant state of inflammation that damages the brain. The researchers recently developed a way to measure levels of amyloid beta-RAGE complex, and preliminary data using transgenic mice that express Alzheimer's symptoms suggest that an antigen they created to boost the body's natural immune response to the complex can reduce the formation of the brain plaques.

"The amyloid beta-RAGE complex cuts off the connections between neurons," Mruthinti explained, "but our hope is that we can protect those connections by preventing those plaques from forming."
References:
1. Stephen Miller, et al. University of Georgia.