Antibody & Alzheimer's

Significant elevations of antibodies in Alzheimer's patients could lead to its early diagnosis.

Researchers at the Medical College of Georgia and Veterans Affairs Medical Center in Augusta have found significant elevations of certain antibodies in Alzheimer's patients, a finding that could lead to early diagnosis and more targeted treatment.

The ability to measure these specific antibody levels could lead to a method for early diagnosis of the disease when treatment has the most potential and even help identify those at risk, claim the lead researchers Drs. Shyamala Mruthinti and Jerry J. Buccafusco.

The finding could also enable development of a monoclonal antibody that selectively destroys the deadly protein-receptor combination. They also support the theory that autoimmunity and resulting inflammation play a big role in the destructive brain disease.

"This is one of the most exciting papers I have ever participated in," says Dr. Buccafusco, pharmacologist and director of the MCG Alzheimer's Research Center.

Amyloid-_ peptide is a protein fragment, which is harmless as long as it is circulating in the bloodstream. The same can be said for RAGE peptide, another natural human product that actually can help attract cellular garbage in the bloodstream, such as beta amyloid, and remove it from the body.

"We have shown that advanced glycation end products in the presence of beta amyloid enhance the expression of specific cellular receptors such as RAGE that are known to bind the toxic form of amyloid," Dr. Mruthinti says.

She and Dr. Buccafusco began dissecting the relationship between RAGE and beta amyloid after immunizing laboratory mice with advanced glycation end products in pursuit of a monoclonal antibody that might be a diagnostic marker for Alzheimer's.

"It seems that when the mice were immunized, this enhanced the presence of circulating RAGE peptide which, in turn, formed the highly immunogenic complex with beta amyloid protein," Dr. Mruthinti said.

Activation of the immune system by the resulting complex has shown that there is an autoimmune component to the disease.

The researchers also found a linear correlation: when amyloid-antibodies were high, so were RAGE antibodies, probably because they are binding to the same complex.

"What we want to do is find patients who have the propensity of becoming Alzheimer's patients. That is where a simple, early diagnostic test would come in handy. If you could tell someone they have a high chance of becoming an Alzheimer's patient in the next five to 10 years, then you can keep an eye on them and intervene early in the disease when it will do the most good," Dr. Buccafusco added.