Study Further Links Brain Cell Deprivation to Alzheimer's Disease

Alzheimer's Association
Wednesday, 13 March 1996

A study that reports a newly discovered role for an abnormal protein (beta-amyloid) linked to Alzheimer's disease also advances a new theory relating beta-amyloid to blood vessel abnormalities that interfere with the brain's energy supply, according to the Alzheimer's Association.

"The findings of this study are a different aspect of the problem reported in Nature Medicine about triplet repeat genes causing something approximating an 'energy crisis' in the brain, and leading to several rare neurodegenerative diseases," said Zaven Khachaturian, Ph.D., director of the Alzheimer's Association's Ronald and Nancy Reagan Research Institute. "This could be another mechanism that disrupts the brain's metabolism of energy, which results in cell dysfunction and death."

According to Khachaturian, this study indicates another possible detrimental role for beta-amyloid, and highlights the importance of studying the blood supply to the brain, something we know very little about.

"We must caution that this new work, however intriguing, was done with isolated blood vessels in a test tube," Khachaturian said. "We don't know yet if these findings are true in a living, functioning human brain."

The goal of the Reagan Institute, launched by the Association in November 1995, is to accelerate the discovery and development of treatments and preventions for Alzheimer's disease by increasing information exchange, technology transfer and alliances among investigators.

The study, "B-Amyloid-mediated vasoactivity and vascular endothelial damage," by Michael Mullan, M.D., Ph.D., Thomas Thomas, M.D., Ph.D., and colleagues at Roskamp Laboratories at the University of South Florida, is published in the March 14, 1996 issue of Nature. Mullan received a 1995 Investigator-Initiated Research Grant from the Alzheimer's Association to study a gene on chromosome 14 linked to early-onset Alzheimer's disease.

The study shows that the protein, beta-amyloid, the primary component of one of the brain lesions associated with Alzheimer's disease, appears to cause constriction of blood vessels. The constriction is caused by the generation of toxic free radicals as the beta-amyloid interacts with certain cells on the blood vessels. The researchers suggest this could increase the amount of free radicals and lower the amount of blood available to the brain. The result is brain cell death caused by the reduced amount of available oxygen and glucose, thus starving the brain of essential nutrients. Free radicals also cause the death of brain cells.

Scientists were able to prevent the blood vessels from constricting by pre-treating them with antioxidants, which are substances, such as vitamin E, that eliminate free radicals. They suggest this as a possible new therapeutic approach to Alzheimer's disease.

"If the findings are correct, we could focus on developing compounds that would counteract the constricting effects of the beta-amyloid on blood vessels," Khachaturian said.

For more information, or to contact Alzheimer's Association, see their website at: www.alz.org