New Theory About Cause of Brain Cell Damage

Alzheimer's Association
Monday, 25 May 1998

In a new study, researchers suggest a novel theory about how brain cells die in Alzheimer's disease and provide possible new targets for drug therapies, according to the Alzheimer's Association.

The scientists report that small clumps of a protein called beta amyloid killed cells in mouse brains. Larger accumulations of beta amyloid protein, known as plaques, are one of the two characteristic brain lesions in Alzheimer's disease in humans.

While reinforcing a role for amyloid in Alzheimer's, the new findings suggest that, in addition to the effects of full-blown plaques, smaller fragments of beta amyloid are toxic, perhaps early in the disease process. One long-standing hypothesis says amyloid plaques are the cause of brain cell dysfunction and death in Alzheimer's disease, though this remains unproven.

"This finding may be related to the earliest harmful effects of Alzheimer's disease, and, if shown to occur in human brains, would be a prime target for therapies to stop the damage," said Steven DeKosky, M.D., director of the Alzheimer's Disease Center at the University of Pittsburgh and chair of the association's Medical and Scientific Advisory Council.

"Diffusible, nonfibrillar ligands derived from Ab 1-42 are potent central nervous system neurotoxins," by William Klein, Ph.D., professor of Neurobiology and Physiology at Northwestern University, Evanston, Ill., and colleagues, appeared in the May 26, 1998 issue of The Proceedings of the National Academy of Sciences. The study was funded, in part, by the Alzheimer's Association. According to the association, the study needs to be confirmed and, more importantly, it needs to be shown that the findings are true in human beings.

In the study, the scientists further suggest that the clumps, known as ADDLs, have adverse effects on the functioning of brain cells before damaging or killing them. The researchers speculate that, if ADDLs prove to be destructive to human brain cells in Alzheimer's, it may be possible to find or develop drugs that block nerve cell injury and allow for the recovery of normal functioning or cessation of decline.

"This study provides intriguing possibilities for the future, and it reinforces the mission of the Alzheimer's Association to accelerate the discovery of treatments for Alzheimer's disease. But, it is important to note the reality that such discoveries may take years before they are translated to human use," said Zaven Khachaturian, Ph.D., director of the association's Ronald & Nancy Reagan Research Institute.

The Association recently awarded one of its T.L.L. Temple Foundation Discovery Awards to another key researcher on the project, Grant Krafft, Ph.D., director of research development at Evanston Northwestern Healthcare in Evanston, IL, and professor of Neurology at Northwestern University. Krafft will receive $250,000 over two years for research to screen compounds for possible candidates to protect brain cells from ADDLs, without inducing adverse effects on memory or other brain functions.

Without a medical breakthrough before the baby boomers reach the age of highest risk, 14 million Americans could be afflicted by the year 2050. The Association is calling on Congress to appropriate an additional $100 million to the National Institutes of Health this year for Alzheimer's disease research.

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