FAQ: New Alzheimer‘s Gene

June 27, 2008 -- Scientists have discovered a new Alzheimer's disease gene called CALHM1.

That genetic risk factor is common, and while it's not as big a risk as another genetic variant called ApoE4, it is "extremely significant" and may lead to new Alzheimer's treatments, researcher Philippe Marambaud, PhD, tells WebMD.

What does the new Alzheimer's gene mean for Alzheimer's treatment? Should you get a genetic test for CALHM1? WebMD spoke with Marambaud to get answers.

Maramboud works at the Feinstein Institute for Medical Research in Manhasset, N.Y. and is an assistant professor of pathology at New York's Albert Einstein College of Medicine.

Marambaud and colleagues -- including Fabian Campagne, PhD, of Cornell University's Weill Medical College -- report their discovery of CALHM1 in Cell.

What would you want people to know about your findings?

The basic finding is related to the identification of a new genetic risk factor for late-onset Alzheimer's disease. What is late-onset Alzheimer's disease? This represents the vast majority of the Alzheimer's disease cases, occurring on average after 65 years old.

This is a very important genetic risk factor that is found in about 23% of the overall population. If you carry one copy of this risk allele -- this may be a bit technical -- let's say one copy of this factor, the risk is increased 44% . And if you carry two copies, the risk is increased 77%.

So this is an important risk factor. It's not as robust as the so-called ApoE4 risk factor, which increases the risk threefold if you carry one copy of this risk factor. But it is found in more individuals than ApoE4, so it is extremely significant.

Do we know anything about what that variant does?

Yes. We have provided very strong evidence in this recent publication that this risk factor is found in a gene that represents a new calcium channel. A calcium channel is a protein that allows entry into the cells, and in this case, we believe into the neurons, of the calcium ion. Calcium ions are very important signals inside the cells to generate a mechanism related to memory formation, for instance.

But also, what we found is that these signals lead to the modulation of the so-called APP processing. The APP processing is a very important pathway that leads to the production of the amyloid peptide. The amyloid peptide is a building block of senile plaque. There is a hypothesis right now in the field that amyloid plaque, but also amyloid peptides before they aggregate into plaque, may be the toxic element in the disease.

So basically, we found a link between the genetics of the disease, with this susceptibility factor, and the production of the amyloid peptides, which is very important.