Establishing a connection

Researchers at the Byrd Alzheimer’s Institute and the Florida Alzheimer’s Disease Research Center, both located at USF, are working together to examine the link between Alzheimer’s disease and Down syndrome.

The two centers, which work in conjunction with similar centers across the state, are “a consortium of researchers put together to attack the problem of Alzheimer’s disease,” said Huntington Potter, Eric Pfeiffer chair for Alzheimer’s research at USF’s College of Medicine. Potter is also the CEO and scientific director of the Byrd Alzheimer’s institute.

The link between Alzheimer’s and Down syndrome has been established through trisomy 21, the name for the process that occurs when chromosome 21 produces three copies of itself instead of two. Those who have trisomy 21 — Down syndrome patients and some Alzheimer’s patients — have increased production of Abeta1—42, which is the peptide that forms the Alzheimer’s plaques on the brain.

“Abeta accumulation and inflammation are both characteristics of Alzheimer’s disease and Down syndrome,” Potter said.

Trisomy 21 causes “Abeta1—42 (to be) deposited and not cleared out of the brain properly. Abeta can be soluble or insoluble,” said Amy Borenstein, a USF professor in the department of epidemiology and biostatistics in the College of Public Health.

“Soluble (Abeta) is not a problem, but insoluble is. (People who have the trisomy) are cranking out 50 percent more of this Abeta1—42. Insoluble Abeta sticks together and clumps in the brain and causes the destruction of neurons,” Borenstein said.

Potter and his team discovered several years earlier that trisomy 21 cells were present in some Alzheimer’s patients. These findings were confirmed by two different labs, Potter said.

“Normal Alzheimer’s patients who are elderly actually have Down syndrome cells (trisomy 21) that they have developed during their life,” Potter said. “We have proven the fact that they have cells (of trisomy 21, also found in Down syndrome patients). The mechanism by which they develop those cells is being investigated.”

There are various possibilities contributing to the development of trisomy 21 in Alzheimer’s patients that the researchers are investigating.

“We think it might be partly environmental, (or) mutated forms of some genes. Aluminum was thought to be a factor, but the data did not support the hypothesis,” Potter said.

The development of the trisomy of Alzheimer’s patients earlier in their lifetime, Potter said, may be due improper cell growth and division.

“Every time a cell grows in a developing organism,” he said, “it has the chance of making a mistake. That’s called chromosome missegregation.”

Potter said that, “it’s possible that you can reach the same endpoint (of Alzheimer’s) by an extremely different mechanism, something that could create more Abeta. That’s the general idea of how Alzheimer’s develops. What we’re suggesting (through our research of trisomy 21) is that’s not the only way (that more Abeta is created).”

In Down syndrome patients, eggs in older mothers usually cause the trisomy 21 to occur.

“Early on, it was shown that Alzheimer’s patients (who) had mothers that were older (had) a risk factor for Down syndrome,” Borenstein said. “The mothers were either a little bit younger than the controls or a little bit older. If you’re going to have a kid past 35, they want you to get a test for Down syndrome. They line up all your chromosomes to see if you have an extra 21.”

Age is a factor in Alzheimer’s; it is also a factor in Down syndrome. As someone with Down syndrome ages, his or her risk of developing Alzheimer’s increases correspondingly.

“The risk of developing Alzheimer’s in Down syndrome patients is high and the risk increases 30 years earlier than in people who do not have Down syndrome,”Borenstein said.

Rick Wilber, a mass communications professor at USF, has two family members at different ends of the spectrum of the struggle: His mother has Alzheimer’s, and his son, who is in his mid-30s, has Down syndrome.

“Like all parents of Down syndrome people, we sort of keep an eye on Alzheimer’s research,” Wilber said. “As modern medicine begins to find ways to treat Alzheimer’s people, (it becomes clearer) that there may be ways to treat Down syndrome. Down syndrome people clearly have a predisposition to Alzheimer’s.

“Mom has responded well to a drug called Aricept,” Wilber continued. “These drugs don’t help make anyone better, but they slow the progress of the disease. Some of us have wondered whether it would be a good idea to get Down syndrome people on Aricept. Most Down syndrome people did not live long enough to encounter this problem.”

Potter said that, “in the long run, it’s quite possible that drugs that are being developed for Alzheimer’s can help the Down syndrome patients who are showing symptoms of Alzheimer’s.”

Wilber said that those with Down syndrome “are interesting, complex, very special people. They’re often outgoing, gregarious and happy. Many of them are smart enough to know how smart they’re not. My son has done so much better than the experts said he would. I am so proud of him and what he’s done with his life.”