Martin Westwell

Whatever happened to the Alzheimer's vaccine?

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.

- July 2004