Alzheimer's Disease: New Theory on How Damages the Brain

Study reveals early events in the disease, new targets for treatment

Tuesday, January 7, 2003

In a study out today in the Proceedings of the National Academy of Sciences, researchers at Brigham and Women's Hospital (BWH) suggest that the brain damage central to the progression of Alzheimer's Disease (AD) may start far earlier than previously thought, and be caused by newly implicated protein molecules.

Studies have shown that the build-up in the brain of certain toxic proteins, called amyloids, leads to the emergence of the disease's symptoms. Research has traditionally focused on how to eliminate or lower the levels of these proteins in the brain as a potential treatment for the disease.

But now researchers from BWH and the Massachusetts Institute of Technology (MIT) believe that the memory loss associated with the disease begins long before protein deposits collect in the brain, and that a new understanding of how the disease progresses may have an important impact on how AD is treated in the future.

"Until now, we knew these proteins were toxic, but we had little understanding of how they formed toxic structures," said David Teplow, PhD, BWH, senior author of the study. "Our new studies show that in the most damaging form of Alzheimer's Disease, amyloid protein sticks together in a very distinct way, producing structures that enhance toxicity."

In their work, which did not involve human subjects, Teplow, lead author Gal Bitan, PhD, BWH, and MIT collaborators Aleksey Lomakin, PhD, and Professor George Benedek, determined that the amyloid protein associated with Alzheimer's Disease binds to itself to form larger, more damaging structures known as oligomers. These oligomers then form structures resembling beads on a string, a destructive molecular chain believed to cause nerve cell damage and death.

Approximately four million Americans suffer from AD. The disease is the most common form of dementia in the elderly and gradually erodes intellectual functions and memory.

Teplow said that this new research adds credibility to an increasing body of evidence that suggests fibrils, twisted ropes of amyloid protein that clog cells, may not be as damaging as the oligomer strings of the most toxic proteins.

"We are closer to understanding just how AD develops in the brain, and that of course gives us new ideas for how to treat the disease," said Teplow. "If we could somehow stop these toxic proteins from forming these beaded structures, we conceivably could slow or stop the disease's progression."

Teplow cautioned, however, that much research still needs to be done with regard to fully understand the pathology of AD.

BWH is a 716-bed nonprofit teaching affiliate of Harvard Medical School and a founding member of Partners HealthCare System, an integrated health care delivery network. Internationally recognized as a leading academic health care institution, BWH is committed to excellence in patient care, medical research, and the training and education of health care professionals. The hospital’s preeminence in all aspects of clinical care is coupled with its strength in medical research. A leading recipient of research grants from the National Institutes of Health, BWH conducts internationally acclaimed clinical, basic and epidemiological studies.

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