Protein 'Pump' May Aid in Alzheimer's Prevention

A protein well known to scientists appears to clear the brain of amyloid beta, the main component of the plaques that are found in Alzheimer's patients, according to a new study with mice.

The protein, P-glycoprotein (Pgp), has long been known to obstruct chemotherapy drugs and other drugs used in treating brain disorders. But, by creating drugs that alter the natural levels of Pgp, it may be possible to prevent and treat Alzheimer's disease, the researchers suggest.

"We found a new way of getting amyloid out of the brain," said lead author John Cirrito, a postdoctorate research fellow at Washington University School of Medicine in St. Louis. "Now there are avenues we can explore to try to find a treatment. Anything you can do to prevent amyloid beta from being produced or helping get it cleared is good."

The study findings appear Oct. 20 in the online edition of the Journal of Clinical Investigation.

Pgp is one of several molecular transporters that form the blood-brain barrier, a layer of cells that limits the ability of many types of molecules -- including many drugs -- to enter the brain through the circulatory system, Cirrito said. "In the blood-brain barrier, it normally acts to keep molecules out of the brain," he explained, adding the protein actually pumps molecules out of brain cells.

Earlier research had hinted that Pgp could also transport amyloid beta molecules out of the brain, Cirrito said. "We basically show that if we inject amyloid beta into the brains of mice, Pgp can pump amyloid beta out of the brain," he said.

The researchers also found that when specially bred mice were given a Pgp inhibitor, amyloid beta levels significantly increased in just a few hours. Also, mice bred not to produce Pgp had higher levels of amyloid beta, compared with mice that were able to make the protein, the researchers said.

Cirrito believes these findings might be used one day to both treat and prevent Alzheimer's disease. "If you could enhance Pgp activity, perhaps you could get amyloid beta out of the brain and not let it build up," he said.

"There are drugs that are used to inhibit Pgp in cancer therapy to help chemotherapy drugs get into tumor cells," Cirrito said. "These inhibitors could make Alzheimer's worse," he noted. There are also common drugs such as statins that inhibit Pgp activity, Cirrito said. And there are compounds, such as St. John's wort, that enhance Pgp activity, he noted.

One expert thinks these findings add to the understanding of how amyloid beta plaque could be removed from the brain.

"This is an exciting paper, and it dovetails well with existing knowledge about the biology of Pgp," said Dr. Sam Gandy, chairman of the Medical and Scientific Advisory Council of the Alzheimer's Association, and director of the Farber Institute for Neurosciences at Thomas Jefferson University in Philadelphia.

There have been fewer studies about how amyloid beta can be removed from the brain than studies examining how it is generated, Grandy said. "But now we can add Pgp to the growing list of molecules that control amyloid beta catabolism," he said.

Grandy thinks this discovery might lead to new treatments for Alzheimer's. Some dietary substances or medications may block Pgp and increase the risk for Alzheimer's disease, while others may enhance the protein, he said.

"It might be possible to develop Pgp modulators that accelerate clearance of amyloid beta in a beneficial way," Gandy said.

More information

To learn more, visit the Alzheimer's Association.

Less Invasive Surgery Works for Sinus Tumors

October 20, 2005 08:41:14 PM PST

Researchers used endoscopy to remove large inverted papillomas in 18 people, aged 36 to 74, and found this method worked well in these patients. Endoscopy was also useful in checking for the re-growth of the tumors, which have a high rate of recurrence. Of the 18 patients, 56 percent remained disease-free 29 months after the procedure.

The study appears in the September/October issue of the American Journal of Rhinology.

With the endoscopic approach, doctors use tiny scopes and cameras to enter the nose and remove the tumor with a device that pulverizes and suctions. At points where the tumor adheres to the sinus lining, the lining is removed and a diamond drill is used to eliminate tumor cells in the underlying bone.

Following the procedure, patients have to take antibiotics and anti-inflammatory drugs, and irrigate their sinuses for a few weeks.

"Operative risk and postoperative morbidity are significantly less than with open procedures. Recurrences are more frequent, but are detected early and are easily resected with minimally invasive techniques," the study authors wrote.

The recurrence rate among the endoscopy patients was 50 percent, compared with the usual recurrence rate of 44 percent among patients who have open procedures.

Open procedures involve large facial incisions and potential complications, including eye loss, cerebral spinal fluid leaks, and disfigurement.

More information

The U.S. National Institute on Deafness and Other Communication Disorders has more about papillomas.

Health Tip: Stay Safe in Your Yard

October 20, 2005 08:41:14 PM PST

While the task may seem like child's play, some outdoor chores can be accidents waiting to happen.

St. John Ambulance Canada offers these safety tips:

• Rake your lawn before you mow to ensure you've collected objects that could become projectiles under the mower blade.
• Give your mower a tune up and perform a safety check before you start it.
• Don't use electrical appliances in wet or damp areas.
• Don't burn debris. There's always the risk of the fire getting out of control.