Can Alzheimer's Disease Be Prevented?

Dementia could be stopped before it starts using genetic research

/ Author:  / Reviewed by: Robert Carlson, M.D

Alzheimer's disease will affect more and more people as the population ages. This disorder slowly robs the old and the not-so-old of their wits and memories, and there is no cure.

Evidence has accumulated that some people inherit genes that increase their risk for the condition. A project is underway to stop the dementia before it starts, by giving drugs to those with genes that are a risk factor for Alzheimer's.

Despite decades of efforts, there is not a clear understanding of the neurological cause of Alzheimer’s. After many millions of dollars spent, countless studies and the efforts of some of the world's best scientists, we can treat the symptoms and alleviate some of the suffering, but not heal the patient.

There has been great interest among scientists in preventing this disease. Now, a never-before attempted project is underway to use genetics to find those at risk for the disorder, and then to give them a drug called crenezumab.

It is possible crenezumab administered to normal people with family histories of the disease may prevent dementia symptoms from occurring.

Can crenezumab cure Alzheimer's?

Scientists are particularly interested in individuals who aren’t yet showing symptoms of the disorder, but who have genes or family histories that predispose them to early-onset Alzhemier's. 

An extensive, multi-year, interdisciplinary initiative to measure the possible preventive benefits of crenezumab is being underaken by teams of researchers associated with the pharmaceutical firm Genentech, the Banner Alzheimer’s Institute and the National Institutes of Health.

The effort will administer crenezumab to 300 individuals who are members of families that have been identified as carrying genes connected to early onset Alzhemier's. The goal is to find out, as stated in a Genentech news release, "if we intervene before cognitive function deteriorates, can we prevent the disease?"

If the answer is yes, it could be a game-changer for those who carry genes increasing risk for Alzheimer's disease. Family histories and gene sequencing could give individuals crucial information about their risk status, and those who are at higher risk could take crenezumab or another beta amyloid-interacting drug.

Plaques, tangles and the biology of dementia

Scientists have examined the atrophied brains of the severely afflicted and found plaques and tangles. Researchers found these are associated with a complex, sticky material called beta amyloid that seems to be more present in the brains of those with the severest symptoms than in normal adults’ brains.

It’s not quite clear whether the plaques and tangles this material forms are the sole or primary cause of the memory problems and other mental deficits seen with Alzheimer's patients. Alternatively, the material might be the result of nerve cells coping with the disease, and thus an effect, not a cause.

Scientists have slowly been discovering certain compounds that interact with the plaques and tangles in potentially therapeutic ways. Laboratory science will have real world medical benefits if crenezumab prevents the formation of the plaques and tangles, and slows or prevents dementia symptoms.

Family history and genes offer clues to Alzhemier's

Researchers have looked at different varieties of Alzheimer's disease. Intriguingly, a minority of patients who are 30 to 60 years old have an early-onset variant. This subtype is more often inherited and called "familial Alzheimer's disease."

Overall, a series of genes on chromosomes connected to the disorder have been discovered, including for the more common common adult-onset Alzheimer's type that generally afflicts those over 60. Family histories and DNA sequencing have added to what is still a very partial understanding of this condition, and researchers hope this will continue as more related genes are found.

Currently, genetic tests can detect genes that affect the likelihood of developing the memory loss and other cognitive problems characteristic of the disorder. However, the National Institutes of Health states, "It is unlikely that genetic testing will ever be able to predict the disease with 100 percent accuracy because too many other factors may influence its development and progression."

Science may never have a completely accurate model of all such factors, but it will be very significant if crenezumab prevents or slows the onset of dementia symptoms for those that genetic tests reveal to be at risk. Those families in Columbia who show an unusual incidence of early-onset Alzheimer's disease may be helping to push scientific knowledge into the new era of genetic medicine.  

Are we near the turning point in the war against Alzhemier's?

The current study will focus on those that family medical studies and genetic tests identify as likely to develop early-onset Alzhemier's. Depending on the results, the much greater population whose symptoms appear in late middle-age or later may also benefit.

Although the researchers are hopeful about where this work will lead, there are no guarantees. Many medications that have interesting and novel properties in the lab turn out to have limited clinical benefits. Likewise, other drugs may work well therapeutically, but also cause serious and debilitating side effects.

The new initiative is still in its early stages. Crenezumab is not available to the public for combating Alzheimer's yet. The MDs, Ph.Ds and others associated with Genentech, Banner Alzheimer’s Institute, and National Institutes of Health teams are being cautious about expectations for this initiative. It is not clear that if Crenezumab can prevent plaques and tangles from forming, or that doing so will stop the decline in memory and other cognitive faculties seen with dementia.

Nonetheless, after so many years of basic research in chemistry, genetics, pharmacology and neurology Alzheimer’s research may be at a turning point. The possibility that medication and genetic tests will support a preventive approach to Alzheimer's inspires researchers, clinicians, patients and family members alike. Within a few years, the world will know whether this project achieves its goal.


Review Date: 
May 21, 2012