Using the Immune System to Fight Alzheimer’s Disease

Our immune system is amazing. It protects us from an ever-changing multitude of foreign invaders that want to colonize our bodies. Parasites, fungi, bacteria, even viruses are repulsed or destroyed by the protective cells of the immune system and the proteins they produce. So it is not surprising that researchers would attempt to activate this powerful ally in the fight against Alzheimer’s disease.

But why does the immune system need activation? Why doesn’t it just attack Alzheimer’s disease on its own?

Basically, the immune system is designed to protect the body from foreign invaders, and is programmed to ignore anything produced by the body itself. Since Alzheimer’s disease involves proteins that are self-produced, the immune system does not normally become involved.

But it is possible to activate an immune response. Sometimes this happens unintentionally. Auto-immune disorders like Muscular Dystrophy, Lupus, and Lou Gehrig’s Disease are abnormal attacks on a body by its own immune system. In these disorders, the immune system has somehow become confused about what is foreign and what is not.

When a researcher wants to activate the immune system against Alzheimer’s disease, they begin with immunization—the same method used when we vaccinate children against polio or mumps, measles, and rubella.

In Alzheimer’s immunization research, small portions of Aβ are injected under the skin along with molecules that irritate the immune system and provoke an immune response. Once the response begins, antibodies are produced that target all the compounds that have been injected. A second injection follows a week or two later. That injection contains only Aβ protein, so all the antibodies made this time will target Aβ.

In Alzheimer’s disease, those antibodies are meant to attack the plaques by attaching to the Aβ and taking it out of circulation before it can form plaques, or by attaching to the plaque itself and marking it for destruction by macrophages (the rubbish trucks of the immune system, macrophages gobble up bacteria, proteins, or plaques that have been pointed out to them by the attachment of antibodies.)

Years ago, Aβ immunization was shown to be amazingly effective in tests on mice, but when tried on humans it caused serious side effects including brain inflammation and even death. Human testing was stopped immediately.

Since then researchers have been working to make “designer antibodies” that will be able to clear away plaques without the negative side effects.

The designer antibodies can be delivered to the brain in two ways:

Active immunization involves actually injecting a person with Aβ that has been modified so the antibodies produced will not be harmful. Active immunization would work like any other vaccination—a few shots, and you would be protected (or treated) for years.

Passive immunization involves growing the designer antibodies in the laboratory (using cell culture techniques) and injecting them periodically. The advantage to passive immunization is that the amount of antibody at work can be carefully controlled. The disadvantage is that it is more costly and involves repeated injections. However, for people who have Alzheimer’s, passive immunization may someday be the treatment of choice. This is because in the elderly, the immune system is not as effective as in the young, and it might not always be possible to reliably activate the immune response.

The true potential of immunotherapy for Alzheimer’s disease remains to be seen, but it is an area of active research and excitement.

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6 thoughts on “Using the Immune System to Fight Alzheimer’s Disease

    • Our understanding is growing so fast it is astounding.
      Twenty years ago, even fifteen years ago, scientists would swear that your potential and your characteristics were determined exclusively by your genetic makeup. Now, the young science of epigenetics has demonstrated conclusively that the circumstances experienced by a mother can affect her unborn child as well as future generations! Amazing stuff.

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  1. What amazing research for Alzheimer’s. When the passive immunizations are approved will it be cost effective? or should I say affordable? Given the physical, mental, and financial drain of the patient and family I would think the cost would be minimal given all the other costs involved with an Alzheimer’s individual. Everyone wants to improve. Thank goodness for this wonderful research.

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    • It is a very exciting area of research. The main improvement seems to come from clearing out small clusters of beta amyloid protein molecules (called oligomers). These are not yet in plaques, but there is much research indicating that it is the oligomers that are the most damaging form of beta-amyloid. A new study even shows these oligomers somehow moving from neuron to neuron as the disease spreads through the brain.
      If they succeed in finding an antibody therapy to clear away those oligomers, it could be a major breakthrough!
      So far, passive immunotherapy is being tested with a number of different designer antibodies. IF one works well and without side effects, I am sure it will be a cost effective option, given the cost of other alternatives.

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