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Researchers Find Another Origin for Alzheimer's

Illness may originate with dividing brain cells, they say

Please note: This article was published more than one year ago. The facts and conclusions presented may have since changed and may no longer be accurate. And "More information" links may no longer work. Questions about personal health should always be referred to a physician or other health care professional.

By Amanda Gardner
HealthDay Reporter

THURSDAY, Jan. 19, 2006 (HealthDay News) -- New findings on the origins of Alzheimer's disease, if confirmed, could turn prevailing theories on their heads, researchers contend.

Scientists reporting in the Jan. 18 issue of the Journal of Neuroscience said the neurodegenerative disease may be triggered when adult nerve cells, or neurons, try to divide.

The work was done in mice and needs to be confirmed in subsequent studies, the researchers stressed. However, the results may provide additional insight into the early cellular events that lead to Alzheimer's in humans.

"It really is going against the central grain of what we know, and it actually may lead to something more promising," said Danilo Tagle, program director in neurogenetics at the U.S. National Institute of Neurological Disorders and Stroke, which sponsored the study.

Other experts are playing down the novelty of the findings. "It's another piece of the puzzle falling into place, but I would not say it debunks other theories," said Maria Carrillo, director of medical and scientific affairs at the Alzheimer's Association. "This particular piece gives more information about what cell division is doing before you get to the disease state."

The prevailing theory of Alzheimer's is that it is caused by a build-up of amyloid plaques in the brain that cause neurons to divide and die.

Cells divide through a process called the "cell cycle." In most cases, neurons usually do not participate in this process, however.

"In regular cells, like in bone and blood, the cells divide. But brain cells do not normally divide," Tagle explained. "The great majority will not divide. The neurons you're born with are pretty much what you have at end of life."

When adult nerve cells do enter this cycle, however, they will die rather than complete the division. "Cells become stuck in the process of cell division," Tagle explained.

The authors of this study, based at Case Western Reserve University's Alzheimer's Disease Center in Cleveland, used mouse models to see if other processes might be at play. To that end, they compared brains cells of three different mouse models of Alzheimer's with brain cells sourced from normal mice.

Alzheimer's mice showed evidence of cell cycling six months before any amyloid plaques showed up, the researchers noted. These neurons also had extra chromosomes, another sign that they had begun to divide. Most of this activity was seen in the cortex and hippocampus regions of the brain, which are most implicated in Alzheimer's.

This would seem to indicate that the formation of amyloid plaques in the brains of Alzheimer's patients is more a byproduct or adjunct of the disease rather than the initiating mechanism.

"The finding would indicate that there are earlier events that are happening that precede the plaque build-up," Tagle said. "The authors have demonstrated in animal models that these changes are happening as early as six months before the first signs of plaque accumulation. This seems to be a separate cellular process unlinked to the plaque process."

"This overturns the central dogma of Alzheimer's disease," Tagle continued. "It opens up the possibility that this is the event that's actually triggering the cells to die. The plaques then would be like red herrings that are a secondary process, and the abnormal cellular process is primary."

The next step will be to see if disrupting the cycle would cause neurons to survive. To that end, the study authors are conducting experiments to see if the painkiller ibuprofen can stop the cell cycle process, and thereby neurodegeneration. Ibuprofen, an anti-inflammatory drug, has been shown to reduce the production of amyloid-beta plaques.

"That would actually lead to less cell death in Alzheimer's, so that would certainly be something that would lessen the impact of the disease," Tagle said.

"This clearly supports the idea that there is more to the story," Carrillo added. "Where exactly those pieces fit, we don't know yet."

More information

For more on Alzheimer's, head to the Alzheimer's Association.

SOURCES: Danilo Tagle, Ph.D., program director, neurogenetics, National Institute of Neurological Disorders and Stroke; Maria Carrillo, Ph.D., director, medical and scientific affairs, Alzheimer's Association; Jan. 18, 2006, Journal of Neuroscience

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