On to the Fountain of Youth

As we've discussed before, variant #4 of the gene that specifies the design of the the apolipoprotein E protein -- APOE4 -- is a significant risk factor for Alzheimer's disease.  If you carry one copy of the gene, your risk of developing Alzheimer's disease is higher than normal, and if you carry two copies it's quite a bit higher.  It's thought that the form of the protein produced using this gene causes or aggravates inflammation which is a key factor in Alzheimer's disease.

Companies that test your DNA will tell you whether or not you carry this gene.  Not carrying this gene does not mean that you won't get the disease, and carrying it doesn't mean that you will.  Nevertheless, we keep our eyes on it.

One question is, why do some people who carry the gene variant not get Alzheimer's disease?  Is it just dumb luck?  Yes, but maybe the luck relates to what other genes may be in your genetic makeup.

In the 1990's researchers discovered the gene klotho, named for the Greek goddess Clotho, a Fate who spins the thread of life.  Like APOE, it has several variants, and the presence of one variant in your genome is associated with longevity.  And so, it's called the longevity gene.  The protein it describes is an enzyme that can influence sensitivity to insulin and also participates in the aging process.  Insulin sensitivity relates to type 2 diabetes, which is another risk factor in Alzheimer's disease.

Some believe that studying klotho can lead to the discovery of ways to control the aging process and significantly extend human life.  Unless Alzheimer's disease gets in the way.

There have been several recent studies trying to understand how klotho might influence the advent and advance of Alzheimer's disease, and its role may be significant.  It might do this by significantly suppressing both oxidation and inflammation in the brain.  These are two major processes in Alzheimer's disease.  

I found this article in Scientific American that addresses how the proteins from APOE4 and klotho might influence Alzheimer's disease.  In fact, I saw another article suggesting that the right combination of klotho variants and APOE4 might have someone with a risk of Alzheimer's disease less than if they did not have APOE4.

It's kind of early to tell if studying klotho will lead us to the Fountain of Youth.  But near-term it can be a real benefit to Alzheimer's researchers.  In studying new drugs, we want to identify test subjects developing the disease long before symptoms begin to present.  So researchers look for people carrying the APOE4 gene variant -- who may or may not develop it.  Weeding people out who carry the helpful klotho variant will significantly increase the probability that your test subjects actually will develop Alzheimer's disease, and you will have more confidence in the test results.