Whatever happened to the Alzheimer's vaccine?

07 July 2004
Posted by Martin Westwell.

In February this year a clinical trial testing a vaccination against Alzheimer's Disease was dealt a crushing blow when some of patients showed side effects of brain inflammation. The trial was stopped and it looked like the great hope of an Alzheimer's vaccine was lost.

The immunologists weren't to be beaten so easily. The trial might have failed, but many scientists still believe that the human immune system can be trained to fight off Alzheimer's Disease by attacking the beta-amyloid peptide. This peptide is a short chain of amino acids (up to 42) like a molecular string of beads. When they are produced in the brain during Alzheimer's Disease the peptides all line up and stick together causing hard, microscopic chunks called amyloid plaques to appear in the brain. Many scientists believe that either the peptides themselves or the microscopic amyloid plaques actually cause the damage to the brains of patients with Alzheimer's Disease. The thinking goes that if an individual's immune system can be trained to attack the peptides (whether individually or in the plaques) then perhaps they will be protected against the damage the peptides may cause to the brain that leads to Alzheimer's.

At first it was thought that the vaccine worked by prompting the immune system to make antibodies that would actually get into the brain and attack the peptides where they lay. This may be the case, but the brain protects itself from invasion by preventing large molecules like antibodies from passing through the so called blood-brain barrier. Indeed, one of the first things you may expect to see if the brain were invaded in this way would be inflammation. More recent research has suggested that there may be an exchange of the peptides between the brain and the blood, so that if the antibodies in the bloodstream can attack the peptides here, more peptides will seep out of the brain only to be attacked themselves. If this is the case then the blood would be acting as a kind of waste disposal where the peptides would be destroyed and then more peptides fed in from the brain.

If we are to have an effective vaccine against Alzheimer's Disease there are many questions that will need to be answered. Do the peptides actually cause the Disease? Does the antibody enter the brain or do its work in the bloodstream? Is it safe to inject people with a substance that is very similar to the neurotoxic beta-amyloid peptide? This is one aspect of science at its best - asking and answering the questions that may have a real impact on the lives of millions of people.

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