A study of the genetic mechanism behind acne inversa — a skin disorder that can look similar to other types of acne but shows up only in areas such as the armpit and inner thigh — provides new insight into the development of early-onset familial Alzheimer’s disease.

Mutations in a gene, called PSEN1, believed to cause familial Alzheimer’s may also cause acne inversa, the researchers said. Interestingly, the scientists found the mutations that cause each disease are distinct, and the two diseases might be mutually exclusive.

Though both Alzheimer’s and acne inversa appear to be caused by mutations in PSEN1, there have not been any reported cases of both diseases occurring together, the researchers said. None of the fifty subjects in the new study exhibited symptoms of Alzheimer’s disease or dementia .

“We were surprised that PSEN1 mutations caused acne inversa, but got even more excited after realizing” the mutations were in the same gene as the mutations linked to Alzheimer’s disease, said study researcher Xue Zhang, of Peking Union Medical College in Beijing.

The study, done in China, is published online today (Oct. 7) in the journal Science.

Finding the link

The researchers examined the genes of fifty people between the ages of 15 and 81, all from six Chinese families affected by acne inversa over several generations. The researchers found mutations in PSEN1 in these people, but found no such mutations in the 200 people they also tested who did not have the acne condition .

PSEN1 had previously been linked to the development of early-onset Alzheimer’s — scientists have found more than 160 mutations in PSEN1. The mutations affect a protein called gamma-secretase, which is involved in the build-up of protein plaques in the brains of people with Alzheimer’s disease.

Although future studies would need to confirm Zhang’s findings, the results hint at the possibility that people with acne inversa are somehow protected from early-onset Alzheimer’s disease.

“It’s an interesting question, but so far we have no answer,” Zhang said.

Treatments for both conditions

In any case, Zhang said, just as the protein gamma-secretase has been a target for developing drugs to treat Alzheimer’s disease, it may also be a good target for acne inversa treatments. And because different mutations in PSEN1 cause both diseases, the drugs may in fact work more effectively for acne inversa patients.

So far, drugs targeting gamma-secretase have not performed well in Alzheimer’s patients in clinical trials. For example, Eli Lilly’s drug semagacestat (also called LY450139), perhaps the most promising of these drugs, performed so poorly the company halted Phase 3 clinical trials of the drug in August.

In early studies, the drug reduced brain plaques, but in the larger, Phase 3 studies, semagacestat “was associated with worsening of clinical measures of cognition,” according to a statement from Eli Lilly and Company.

Zhang’s study indicates the type of PSEN1 mutation involved may lead to very different diseases.

“Skin might be more sensitive to changes in gamma-secretase activity,” Zhang told My Health News Daily, “and the mutations associated with Alzheimer’s disease might have a distinct pathogenic mechanism.”

Some researchers have said instead of targeting gamma-secretase itself, Alzheimer’s drugs should target proteins that affect its activity. Last month, researchers reported in the journal Nature an average 38 percent reduction of Alzheimer’s plaques in the brains of mice treated with an inhibitor of a protein that activates gamma-secretase. Blocking the activity of its activator may be a better way to target this protein, the researchers said.

Such treatments could also reduce side effects, because gamma-secretase regulates other pathways important for normal cell function.

“There are many unanswered questions,” Zhang said. “We don’t know why mutations in the gamma-secretase genes cause these different diseases.”

Next, Zhang plans to research other genes that may cause different forms of acne inversa.