Home > News

THURSDAY, April 15 (HealthDayNews) -- Researchers may have managed to connect two "dots" in the biology of Alzheimer's disease that could eventually lead to new drug therapies.

Two areas of Alzheimer's research have received much attention but their relationship to each other has been unclear, explained Dr. Sam Gandy, vice president of the Alzheimer's Association's Medical and Scientific Advisory Council. One is the characteristic and toxic build-up of amyloid beta protein in the brain of Alzheimer's patients. The other is a disturbance in the energy metabolism of nerve cells that is controlled by the cellular structure known as mitochondria.

A new paper appearing in the April 16 issue of Science proposes that the amyloid beta protein somehow invades the mitochondria and disrupts their energy-producing function. Exactly how the protein manages to overcome a cell's defenses to do this remains unclear, though.

"It's exciting in that it would link two apparently disparate parts of the research," said Gandy, who is also director of the Farber Institute for Neurosciences at Thomas Jefferson University in Philadelphia. "But I still consider it to be somewhat preliminary."

An estimated 4.5 million Americans have Alzheimer's disease, which results in the progressive loss of mental functioning, including memory, and can eventually prove fatal.

The authors of the new study speculated that amyloid beta protein interacted with an enzyme called ABAD in the mitochondria to produce the disruption in the mitochondria.

They managed to show this interaction, both in genetically engineered mice and in brain tissue from people who had died of Alzheimer's. The interaction caused damage to not just the mitochondria but the entire nerve cell. Eventually the nerve cells died, resulting in the symptoms associated with Alzheimer's.

"The mechanisms of the cause of neuronal damage have been quite unclear, so in our study we show that amyloid beta protein accumulates in the mitochondria in transgenic mice and interacts with one protein we call ABAD to produce toxicity," said Dr. Shi Du Yan. She is lead author of the study and an associate professor of clinical pathology at the College of Physicians & Surgeons at Columbia University in New York City.

"This is perhaps one of the first studies that shows that beta amyloid can act on the mitochondria to induce toxicity," added Hao Wu, co-senior author of the study and a professor of biochemistry and structural biology at Weill Medical College of Cornell University, also in New York City.

One remaining question, however, is how the protein makes its way into the mitochondria. "No one knows how it gets there," Wu said.

Still, Wu and her colleagues hope that preventing or reducing the interaction between amyloid beta and ABAD may represent an eventual treatment for the disease. "There probably is a potential for treatment," Yan said.

Wu said that when they inhibited the interaction in this study, "we show that amyloid beta can no longer induce cell death," she said. "That says to us that it's playing a major role in beta-induced toxicity."

More information

For more on Alzheimer's, visit the Alzheimer's Association or the Alzheimer's Disease Education and Referral Center.

(SOURCES: Shi Du Yan, M.D., associate professor of clinical pathology, College of Physicians & Surgeons, Columbia University, New York; Hao Wu, Ph.D., professor of biochemistry and structural biology, Weill Medical College of Cornell University, New York; Sam Gandy, M.D., Ph.D., vice president, Medical and Scientific Advisory Council, Alzheimer's Association, and director, Farber Institute for Neurosciences, Thomas Jefferson University, Philadelphia; April 16, 2004, Science)

Copyright © 2004 ScoutNews, LLC. All rights reserved.